PubAnnotation

Id	Subject	Object	Predicate	Lexical cue
TextSentencer_T1	0-71	Sentence	denotes	Decoding protein networks during virus entry by quantitative proteomics
TextSentencer_T1	0-71	Sentence	denotes	Decoding protein networks during virus entry by quantitative proteomics
T12890	0-71	Sentence	denotes	Decoding protein networks during virus entry by quantitative proteomics
TextSentencer_T2	73-81	Sentence	denotes	Abstract
TextSentencer_T2	73-81	Sentence	denotes	Abstract
T29442	73-81	Sentence	denotes	Abstract
TextSentencer_T3	82-212	Sentence	denotes	Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.
TextSentencer_T3	82-212	Sentence	denotes	Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.
T53843	82-212	Sentence	denotes	Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.
TextSentencer_T4	213-421	Sentence	denotes	Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.
TextSentencer_T4	213-421	Sentence	denotes	Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.
T9946	213-421	Sentence	denotes	Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.
TextSentencer_T5	422-499	Sentence	denotes	These interactions are dynamic and frequently involve multiprotein complexes.
TextSentencer_T5	422-499	Sentence	denotes	These interactions are dynamic and frequently involve multiprotein complexes.
T29142	422-499	Sentence	denotes	These interactions are dynamic and frequently involve multiprotein complexes.
TextSentencer_T6	500-738	Sentence	denotes	In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.
TextSentencer_T6	500-738	Sentence	denotes	In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.
T16324	500-738	Sentence	denotes	In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.
TextSentencer_T7	739-984	Sentence	denotes	As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.
TextSentencer_T7	739-984	Sentence	denotes	As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.
T20689	739-984	Sentence	denotes	As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.
TextSentencer_T8	985-1164	Sentence	denotes	Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.
TextSentencer_T8	985-1164	Sentence	denotes	Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.
T41706	985-1164	Sentence	denotes	Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.
TextSentencer_T9	1165-1407	Sentence	denotes	We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.
TextSentencer_T9	1165-1407	Sentence	denotes	We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.
T62877	1165-1407	Sentence	denotes	We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.
TextSentencer_T10	1409-1486	Sentence	denotes	Viruses need to enter permissive host cells in order to propagate and spread.
TextSentencer_T10	1409-1486	Sentence	denotes	Viruses need to enter permissive host cells in order to propagate and spread.
T99277	1409-1486	Sentence	denotes	Viruses need to enter permissive host cells in order to propagate and spread.
TextSentencer_T11	1487-1581	Sentence	denotes	The penetration of cells requires an initial interaction of viral and host surface structures.
TextSentencer_T11	1487-1581	Sentence	denotes	The penetration of cells requires an initial interaction of viral and host surface structures.
T5874	1487-1581	Sentence	denotes	The penetration of cells requires an initial interaction of viral and host surface structures.
TextSentencer_T12	1582-1713	Sentence	denotes	Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.
TextSentencer_T12	1582-1713	Sentence	denotes	Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.
T28063	1582-1713	Sentence	denotes	Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.
TextSentencer_T13	1714-1992	Sentence	denotes	Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .
TextSentencer_T13	1714-1992	Sentence	denotes	Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .
T8637	1714-1992	Sentence	denotes	Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .
TextSentencer_T14	1993-2204	Sentence	denotes	For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.
TextSentencer_T14	1993-2204	Sentence	denotes	For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.
T40365	1993-2204	Sentence	denotes	For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.
TextSentencer_T15	2205-2494	Sentence	denotes	In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .
TextSentencer_T15	2205-2494	Sentence	denotes	In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .
T83209	2205-2494	Sentence	denotes	In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .
TextSentencer_T16	2495-2553	Sentence	denotes	Historically, the first virus receptor found was a glycan.
TextSentencer_T16	2495-2553	Sentence	denotes	Historically, the first virus receptor found was a glycan.
T68800	2495-2553	Sentence	denotes	Historically, the first virus receptor found was a glycan.
TextSentencer_T17	2554-2664	Sentence	denotes	In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .
TextSentencer_T17	2554-2664	Sentence	denotes	In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .
T32807	2554-2664	Sentence	denotes	In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .
TextSentencer_T18	2665-2798	Sentence	denotes	In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.
TextSentencer_T18	2665-2798	Sentence	denotes	In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.
T37788	2665-2798	Sentence	denotes	In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.
TextSentencer_T19	2799-2901	Sentence	denotes	As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.
TextSentencer_T19	2799-2901	Sentence	denotes	As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.
T67553	2799-2901	Sentence	denotes	As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.
TextSentencer_T20	2902-3102	Sentence	denotes	With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .
TextSentencer_T20	2902-3102	Sentence	denotes	With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .
T52334	2902-3102	Sentence	denotes	With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .
TextSentencer_T21	3103-3358	Sentence	denotes	Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .
TextSentencer_T21	3103-3358	Sentence	denotes	Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .
T65342	3103-3358	Sentence	denotes	Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .
TextSentencer_T22	3359-3506	Sentence	denotes	Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.
TextSentencer_T22	3359-3506	Sentence	denotes	Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.
T99710	3359-3506	Sentence	denotes	Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.
TextSentencer_T23	3507-3629	Sentence	denotes	Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.
TextSentencer_T23	3507-3629	Sentence	denotes	Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.
T69360	3507-3629	Sentence	denotes	Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.
TextSentencer_T24	3630-3646	Sentence	denotes	Attach- surface.
TextSentencer_T24	3630-3646	Sentence	denotes	Attach- surface.
T50255	3630-3646	Sentence	denotes	Attach- surface.
TextSentencer_T25	3647-3805	Sentence	denotes	Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).
TextSentencer_T25	3647-3805	Sentence	denotes	Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).
T78720	3647-3805	Sentence	denotes	Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).
TextSentencer_T26	3806-3959	Sentence	denotes	Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.
TextSentencer_T26	3806-3959	Sentence	denotes	Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.
T41393	3806-3959	Sentence	denotes	Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.
TextSentencer_T27	3960-4089	Sentence	denotes	A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .
TextSentencer_T27	3960-4089	Sentence	denotes	A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .
T14668	3960-4089	Sentence	denotes	A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .
TextSentencer_T28	4090-4204	Sentence	denotes	For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.
TextSentencer_T28	4090-4204	Sentence	denotes	For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.
T76750	4090-4204	Sentence	denotes	For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.
TextSentencer_T29	4205-4289	Sentence	denotes	In some cases host proteases interact with and cleave VAPs rendering them fusogenic.
TextSentencer_T29	4205-4289	Sentence	denotes	In some cases host proteases interact with and cleave VAPs rendering them fusogenic.
T53591	4205-4289	Sentence	denotes	In some cases host proteases interact with and cleave VAPs rendering them fusogenic.
TextSentencer_T30	4290-4394	Sentence	denotes	PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.
TextSentencer_T30	4290-4394	Sentence	denotes	PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.
T19124	4290-4394	Sentence	denotes	PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.
TextSentencer_T31	4395-4476	Sentence	denotes	Classical virus infection pathways are illustrated for a generic enveloped virus.
TextSentencer_T31	4395-4476	Sentence	denotes	Classical virus infection pathways are illustrated for a generic enveloped virus.
T38807	4395-4476	Sentence	denotes	Classical virus infection pathways are illustrated for a generic enveloped virus.
TextSentencer_T32	4477-4620	Sentence	denotes	Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).
TextSentencer_T32	4477-4620	Sentence	denotes	Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).
T22370	4477-4620	Sentence	denotes	Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).
TextSentencer_T33	4621-4700	Sentence	denotes	PPIs facilitating virus attachment, surfing, fusion and transport are depicted.
TextSentencer_T33	4621-4700	Sentence	denotes	PPIs facilitating virus attachment, surfing, fusion and transport are depicted.
T35485	4621-4700	Sentence	denotes	PPIs facilitating virus attachment, surfing, fusion and transport are depicted.
TextSentencer_T34	4701-4794	Sentence	denotes	In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.
TextSentencer_T34	4701-4794	Sentence	denotes	In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.
T81601	4701-4794	Sentence	denotes	In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.
TextSentencer_T35	4795-4934	Sentence	denotes	Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.
TextSentencer_T35	4795-4934	Sentence	denotes	Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.
T91634	4795-4934	Sentence	denotes	Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.
TextSentencer_T36	4935-5026	Sentence	denotes	Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.
TextSentencer_T36	4935-5026	Sentence	denotes	Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.
T88841	4935-5026	Sentence	denotes	Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.
TextSentencer_T37	5027-5169	Sentence	denotes	The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .
TextSentencer_T37	5027-5169	Sentence	denotes	The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .
T82857	5027-5169	Sentence	denotes	The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .
TextSentencer_T38	5170-5355	Sentence	denotes	Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .
TextSentencer_T38	5170-5355	Sentence	denotes	Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .
T86845	5170-5355	Sentence	denotes	Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .
TextSentencer_T39	5356-5526	Sentence	denotes	After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .
TextSentencer_T39	5356-5526	Sentence	denotes	After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .
T29961	5356-5526	Sentence	denotes	After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .
TextSentencer_T40	5527-5686	Sentence	denotes	Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.
TextSentencer_T40	5527-5686	Sentence	denotes	Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.
T78499	5527-5686	Sentence	denotes	Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.
TextSentencer_T41	5687-5778	Sentence	denotes	Transport relies again on PPI of virus structural proteins and microtubular motor proteins.
TextSentencer_T41	5687-5778	Sentence	denotes	Transport relies again on PPI of virus structural proteins and microtubular motor proteins.
T14100	5687-5778	Sentence	denotes	Transport relies again on PPI of virus structural proteins and microtubular motor proteins.
TextSentencer_T42	5779-5917	Sentence	denotes	All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.
TextSentencer_T42	5779-5917	Sentence	denotes	All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.
T79897	5779-5917	Sentence	denotes	All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.
TextSentencer_T43	5918-6052	Sentence	denotes	Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.
TextSentencer_T43	5918-6052	Sentence	denotes	Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.
T72564	5918-6052	Sentence	denotes	Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.
TextSentencer_T44	6053-6142	Sentence	denotes	Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.
TextSentencer_T44	6053-6142	Sentence	denotes	Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.
T89371	6053-6142	Sentence	denotes	Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.
TextSentencer_T45	6143-6211	Sentence	denotes	In brief, most processes during virus entry are coordinated by PPIs.
TextSentencer_T45	6143-6211	Sentence	denotes	In brief, most processes during virus entry are coordinated by PPIs.
T96058	6143-6211	Sentence	denotes	In brief, most processes during virus entry are coordinated by PPIs.
TextSentencer_T46	6212-6376	Sentence	denotes	In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.
TextSentencer_T46	6212-6376	Sentence	denotes	In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.
T72320	6212-6376	Sentence	denotes	In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.
TextSentencer_T47	6377-6601	Sentence	denotes	Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .
TextSentencer_T47	6377-6601	Sentence	denotes	Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .
T18904	6377-6601	Sentence	denotes	Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .
TextSentencer_T48	6602-6757	Sentence	denotes	Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.
TextSentencer_T48	6602-6757	Sentence	denotes	Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.
T93501	6602-6757	Sentence	denotes	Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.
TextSentencer_T49	6758-6886	Sentence	denotes	In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.
TextSentencer_T49	6758-6886	Sentence	denotes	In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.
T543	6758-6886	Sentence	denotes	In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.
TextSentencer_T50	6887-7039	Sentence	denotes	The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .
TextSentencer_T50	6887-7039	Sentence	denotes	The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .
T84284	6887-7039	Sentence	denotes	The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .
TextSentencer_T51	7040-7189	Sentence	denotes	Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.
TextSentencer_T51	7040-7189	Sentence	denotes	Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.
T464	7040-7189	Sentence	denotes	Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.
TextSentencer_T52	7190-7295	Sentence	denotes	Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.
TextSentencer_T52	7190-7295	Sentence	denotes	Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.
T49143	7190-7295	Sentence	denotes	Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.
TextSentencer_T53	7296-7445	Sentence	denotes	Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.
TextSentencer_T53	7296-7445	Sentence	denotes	Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.
T94739	7296-7445	Sentence	denotes	Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.
TextSentencer_T54	7446-7758	Sentence	denotes	Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:
TextSentencer_T54	7446-7758	Sentence	denotes	Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:
T77542	7446-7758	Sentence	denotes	Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:
TextSentencer_T55	7759-7804	Sentence	denotes	Definitions and abbreviations in virus entry.
TextSentencer_T55	7759-7804	Sentence	denotes	Definitions and abbreviations in virus entry.
T54192	7759-7804	Sentence	denotes	Definitions and abbreviations in virus entry.
TextSentencer_T56	7805-7910	Sentence	denotes	Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.
TextSentencer_T56	7805-7910	Sentence	denotes	Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.
T49236	7805-7910	Sentence	denotes	Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.
TextSentencer_T57	7911-8080	Sentence	denotes	Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.
TextSentencer_T57	7911-8080	Sentence	denotes	Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.
T64260	7911-8080	Sentence	denotes	Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.
TextSentencer_T58	8081-8184	Sentence	denotes	Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.
TextSentencer_T58	8081-8184	Sentence	denotes	Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.
T23061	8081-8184	Sentence	denotes	Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.
TextSentencer_T59	8185-8437	Sentence	denotes	Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.
TextSentencer_T59	8185-8437	Sentence	denotes	Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.
T81179	8185-8437	Sentence	denotes	Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.
TextSentencer_T60	8438-8509	Sentence	denotes	Virus attachment factor: cell surface protein interacting with a virus.
TextSentencer_T60	8438-8509	Sentence	denotes	Virus attachment factor: cell surface protein interacting with a virus.
T29981	8438-8509	Sentence	denotes	Virus attachment factor: cell surface protein interacting with a virus.
TextSentencer_T61	8510-8652	Sentence	denotes	Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.
TextSentencer_T61	8510-8652	Sentence	denotes	Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.
T14346	8510-8652	Sentence	denotes	Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.
TextSentencer_T62	8653-8835	Sentence	denotes	Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.
TextSentencer_T62	8653-8835	Sentence	denotes	Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.
T918	8653-8835	Sentence	denotes	Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.
TextSentencer_T63	8836-8942	Sentence	denotes	Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.
TextSentencer_T63	8836-8942	Sentence	denotes	Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.
T17841	8836-8942	Sentence	denotes	Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.
TextSentencer_T64	8943-9111	Sentence	denotes	Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.
TextSentencer_T64	8943-9111	Sentence	denotes	Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.
T66051	8943-9111	Sentence	denotes	Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.
TextSentencer_T65	9112-9199	Sentence	denotes	Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.
TextSentencer_T65	9112-9199	Sentence	denotes	Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.
T4399	9112-9199	Sentence	denotes	Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.
TextSentencer_T66	9200-9313	Sentence	denotes	VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.
TextSentencer_T66	9200-9313	Sentence	denotes	VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.
T19538	9200-9313	Sentence	denotes	VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.
TextSentencer_T67	9314-9327	Sentence	denotes	Capsid (also:
TextSentencer_T67	9314-9327	Sentence	denotes	Capsid (also:
T10656	9314-9327	Sentence	denotes	Capsid (also:
TextSentencer_T68	9328-9475	Sentence	denotes	Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.
TextSentencer_T68	9328-9475	Sentence	denotes	Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.
T98319	9328-9475	Sentence	denotes	Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.
TextSentencer_T69	9476-9528	Sentence	denotes	The capsid proteins are encoded by the viral genome.
TextSentencer_T69	9476-9528	Sentence	denotes	The capsid proteins are encoded by the viral genome.
T91521	9476-9528	Sentence	denotes	The capsid proteins are encoded by the viral genome.
TextSentencer_T70	9529-9644	Sentence	denotes	Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.
TextSentencer_T70	9529-9644	Sentence	denotes	Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.
T17928	9529-9644	Sentence	denotes	Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.
TextSentencer_T71	9645-9660	Sentence	denotes	Envelope (also:
TextSentencer_T71	9645-9660	Sentence	denotes	Envelope (also:
T20410	9645-9660	Sentence	denotes	Envelope (also:
TextSentencer_T72	9661-9752	Sentence	denotes	Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.
TextSentencer_T72	9661-9752	Sentence	denotes	Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.
T76425	9661-9752	Sentence	denotes	Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.
TextSentencer_T73	9753-9829	Sentence	denotes	The envelope typically displays viral genome encoded transmembrane proteins.
TextSentencer_T73	9753-9829	Sentence	denotes	The envelope typically displays viral genome encoded transmembrane proteins.
T80675	9753-9829	Sentence	denotes	The envelope typically displays viral genome encoded transmembrane proteins.
TextSentencer_T74	9830-10021	Sentence	denotes	These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.
TextSentencer_T74	9830-10021	Sentence	denotes	These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.
T78007	9830-10021	Sentence	denotes	These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.
TextSentencer_T75	10022-10131	Sentence	denotes	Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.
TextSentencer_T75	10022-10131	Sentence	denotes	Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.
T69661	10022-10131	Sentence	denotes	Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.
TextSentencer_T76	10132-10534	Sentence	denotes	Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.
TextSentencer_T76	10132-10534	Sentence	denotes	Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.
T57340	10132-10534	Sentence	denotes	Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.
TextSentencer_T77	10535-10649	Sentence	denotes	Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.
TextSentencer_T77	10535-10649	Sentence	denotes	Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.
T98257	10535-10649	Sentence	denotes	Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.
TextSentencer_T78	10650-10745	Sentence	denotes	Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.
TextSentencer_T78	10650-10745	Sentence	denotes	Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.
T33551	10650-10745	Sentence	denotes	Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.
TextSentencer_T79	10746-10859	Sentence	denotes	(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .
TextSentencer_T79	10746-10859	Sentence	denotes	(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .
T73798	10746-10859	Sentence	denotes	(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .
TextSentencer_T80	10860-11041	Sentence	denotes	Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .
TextSentencer_T80	10860-11041	Sentence	denotes	Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .
T98929	10860-11041	Sentence	denotes	Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .
TextSentencer_T81	11042-11295	Sentence	denotes	While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).
TextSentencer_T81	11042-11295	Sentence	denotes	While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).
T50256	11042-11295	Sentence	denotes	While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).
TextSentencer_T82	11296-11438	Sentence	denotes	Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.
TextSentencer_T82	11296-11438	Sentence	denotes	Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.
T47922	11296-11438	Sentence	denotes	Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.
TextSentencer_T83	11439-11548	Sentence	denotes	Proteomics has already led to the characterization of global cellular alterations induced by virus infection.
TextSentencer_T83	11439-11548	Sentence	denotes	Proteomics has already led to the characterization of global cellular alterations induced by virus infection.
T74571	11439-11548	Sentence	denotes	Proteomics has already led to the characterization of global cellular alterations induced by virus infection.
TextSentencer_T84	11549-11808	Sentence	denotes	For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .
TextSentencer_T84	11549-11808	Sentence	denotes	For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .
T43139	11549-11808	Sentence	denotes	For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .
TextSentencer_T85	11809-12026	Sentence	denotes	Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .
TextSentencer_T85	11809-12026	Sentence	denotes	Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .
T44392	11809-12026	Sentence	denotes	Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .
TextSentencer_T86	12027-12211	Sentence	denotes	Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .
TextSentencer_T86	12027-12211	Sentence	denotes	Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .
T49837	12027-12211	Sentence	denotes	Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .
TextSentencer_T87	12212-12345	Sentence	denotes	Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.
TextSentencer_T87	12212-12345	Sentence	denotes	Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.
T72696	12212-12345	Sentence	denotes	Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.
TextSentencer_T88	12346-12568	Sentence	denotes	As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.
TextSentencer_T88	12346-12568	Sentence	denotes	As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.
T30361	12346-12568	Sentence	denotes	As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.
TextSentencer_T89	12569-12685	Sentence	denotes	Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.
TextSentencer_T89	12569-12685	Sentence	denotes	Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.
T71706	12569-12685	Sentence	denotes	Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.
TextSentencer_T90	12686-12823	Sentence	denotes	The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .
TextSentencer_T90	12686-12823	Sentence	denotes	The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .
T70815	12686-12823	Sentence	denotes	The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .
TextSentencer_T91	12824-13139	Sentence	denotes	Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .
TextSentencer_T91	12824-13139	Sentence	denotes	Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .
T35308	12824-13139	Sentence	denotes	Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .
TextSentencer_T92	13140-13281	Sentence	denotes	Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.
TextSentencer_T92	13140-13281	Sentence	denotes	Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.
T24661	13140-13281	Sentence	denotes	Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.
TextSentencer_T93	13282-13412	Sentence	denotes	To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.
TextSentencer_T93	13282-13412	Sentence	denotes	To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.
T40962	13282-13412	Sentence	denotes	To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.
TextSentencer_T94	13413-13527	Sentence	denotes	Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .
TextSentencer_T94	13413-13527	Sentence	denotes	Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .
T72578	13413-13527	Sentence	denotes	Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .
TextSentencer_T95	13528-13607	Sentence	denotes	Typically, these approaches build on virus overlay protein blot assays (VOPBA).
TextSentencer_T95	13528-13607	Sentence	denotes	Typically, these approaches build on virus overlay protein blot assays (VOPBA).
T2414	13528-13607	Sentence	denotes	Typically, these approaches build on virus overlay protein blot assays (VOPBA).
TextSentencer_T96	13608-13798	Sentence	denotes	VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .
TextSentencer_T96	13608-13798	Sentence	denotes	VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .
T5005	13608-13798	Sentence	denotes	VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .
TextSentencer_T97	13799-13942	Sentence	denotes	Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.
TextSentencer_T97	13799-13942	Sentence	denotes	Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.
T25251	13799-13942	Sentence	denotes	Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.
TextSentencer_T98	13943-14051	Sentence	denotes	In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.
TextSentencer_T98	13943-14051	Sentence	denotes	In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.
T15434	13943-14051	Sentence	denotes	In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.
TextSentencer_T99	14052-14203	Sentence	denotes	A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .
TextSentencer_T99	14052-14203	Sentence	denotes	A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .
T28498	14052-14203	Sentence	denotes	A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .
TextSentencer_T100	14204-14447	Sentence	denotes	The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.
TextSentencer_T100	14204-14447	Sentence	denotes	The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.
T76892	14204-14447	Sentence	denotes	The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.
TextSentencer_T101	14448-14569	Sentence	denotes	However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.
TextSentencer_T101	14448-14569	Sentence	denotes	However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.
T11811	14448-14569	Sentence	denotes	However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.
TextSentencer_T102	14570-14634	Sentence	denotes	Moreover interactions could be lost under denaturing conditions.
TextSentencer_T102	14570-14634	Sentence	denotes	Moreover interactions could be lost under denaturing conditions.
T5119	14570-14634	Sentence	denotes	Moreover interactions could be lost under denaturing conditions.
TextSentencer_T103	14635-14765	Sentence	denotes	An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.
TextSentencer_T103	14635-14765	Sentence	denotes	An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.
T16806	14635-14765	Sentence	denotes	An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.
TextSentencer_T104	14766-14871	Sentence	denotes	This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.
TextSentencer_T104	14766-14871	Sentence	denotes	This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.
T13318	14766-14871	Sentence	denotes	This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.
TextSentencer_T105	14872-15066	Sentence	denotes	For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .
TextSentencer_T105	14872-15066	Sentence	denotes	For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .
T89440	14872-15066	Sentence	denotes	For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .
TextSentencer_T106	15067-15306	Sentence	denotes	Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .
TextSentencer_T106	15067-15306	Sentence	denotes	Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .
T21662	15067-15306	Sentence	denotes	Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .
TextSentencer_T107	15307-15400	Sentence	denotes	Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.
TextSentencer_T107	15307-15400	Sentence	denotes	Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.
T15154	15307-15400	Sentence	denotes	Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.
TextSentencer_T108	15401-15432	Sentence	denotes	In a third (Yan et al., 2012) .
TextSentencer_T108	15401-15432	Sentence	denotes	In a third (Yan et al., 2012) .
T68869	15401-15432	Sentence	denotes	In a third (Yan et al., 2012) .
TextSentencer_T109	15433-15652	Sentence	denotes	Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.
TextSentencer_T109	15433-15652	Sentence	denotes	Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.
T69534	15433-15652	Sentence	denotes	Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.
TextSentencer_T110	15653-15798	Sentence	denotes	A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.
TextSentencer_T110	15653-15798	Sentence	denotes	A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.
T82467	15653-15798	Sentence	denotes	A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.
TextSentencer_T111	15799-15921	Sentence	denotes	To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .
TextSentencer_T111	15799-15921	Sentence	denotes	To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .
T27313	15799-15921	Sentence	denotes	To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .
TextSentencer_T112	15922-16110	Sentence	denotes	Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.
TextSentencer_T112	15922-16110	Sentence	denotes	Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.
T91687	15922-16110	Sentence	denotes	Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.
TextSentencer_T113	16111-16231	Sentence	denotes	In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.
TextSentencer_T113	16111-16231	Sentence	denotes	In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.
T42613	16111-16231	Sentence	denotes	In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.
TextSentencer_T114	16232-16481	Sentence	denotes	It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.
TextSentencer_T114	16232-16481	Sentence	denotes	It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.
T21951	16232-16481	Sentence	denotes	It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.
TextSentencer_T115	16482-16595	Sentence	denotes	A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .
TextSentencer_T115	16482-16595	Sentence	denotes	A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .
T64825	16482-16595	Sentence	denotes	A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .
TextSentencer_T116	16596-16811	Sentence	denotes	Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.
TextSentencer_T116	16596-16811	Sentence	denotes	Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.
T20993	16596-16811	Sentence	denotes	Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.
TextSentencer_T117	16812-16980	Sentence	denotes	Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.
TextSentencer_T117	16812-16980	Sentence	denotes	Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.
T74575	16812-16980	Sentence	denotes	Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.
TextSentencer_T118	16981-17079	Sentence	denotes	High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.
TextSentencer_T118	16981-17079	Sentence	denotes	High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.
T47262	16981-17079	Sentence	denotes	High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.
TextSentencer_T119	17080-17205	Sentence	denotes	Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.
TextSentencer_T119	17080-17205	Sentence	denotes	Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.
T81715	17080-17205	Sentence	denotes	Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.
TextSentencer_T120	17206-17394	Sentence	denotes	However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.
TextSentencer_T120	17206-17394	Sentence	denotes	However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.
T49783	17206-17394	Sentence	denotes	However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.
TextSentencer_T121	17395-17475	Sentence	denotes	Also virus-triggered secondary PPIs are not resolved by these classical methods.
TextSentencer_T121	17395-17475	Sentence	denotes	Also virus-triggered secondary PPIs are not resolved by these classical methods.
T31058	17395-17475	Sentence	denotes	Also virus-triggered secondary PPIs are not resolved by these classical methods.
TextSentencer_T122	17476-17692	Sentence	denotes	The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.
TextSentencer_T122	17476-17692	Sentence	denotes	The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.
T94027	17476-17692	Sentence	denotes	The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.
TextSentencer_T123	17693-17821	Sentence	denotes	In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.
TextSentencer_T123	17693-17821	Sentence	denotes	In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.
T93080	17693-17821	Sentence	denotes	In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.
TextSentencer_T124	17822-18038	Sentence	denotes	In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.
TextSentencer_T124	17822-18038	Sentence	denotes	In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.
T24049	17822-18038	Sentence	denotes	In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.
TextSentencer_T125	18039-18289	Sentence	denotes	Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.
TextSentencer_T125	18039-18289	Sentence	denotes	Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.
T84518	18039-18289	Sentence	denotes	Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.
TextSentencer_T126	18290-18493	Sentence	denotes	Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).
TextSentencer_T126	18290-18493	Sentence	denotes	Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).
T80104	18290-18493	Sentence	denotes	Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).
TextSentencer_T127	18494-18696	Sentence	denotes	LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .
TextSentencer_T127	18494-18696	Sentence	denotes	LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .
T85588	18494-18696	Sentence	denotes	LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .
TextSentencer_T128	18697-18833	Sentence	denotes	Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.
TextSentencer_T128	18697-18833	Sentence	denotes	Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.
T8609	18697-18833	Sentence	denotes	Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.
TextSentencer_T129	18834-18999	Sentence	denotes	To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .
TextSentencer_T129	18834-18999	Sentence	denotes	To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .
T16077	18834-18999	Sentence	denotes	To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .
TextSentencer_T130	19000-19205	Sentence	denotes	This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.
TextSentencer_T130	19000-19205	Sentence	denotes	This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.
T9823	19000-19205	Sentence	denotes	This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.
TextSentencer_T131	19206-19327	Sentence	denotes	Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).
TextSentencer_T131	19206-19327	Sentence	denotes	Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).
T46611	19206-19327	Sentence	denotes	Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).
TextSentencer_T132	19328-19458	Sentence	denotes	Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.
TextSentencer_T132	19328-19458	Sentence	denotes	Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.
T34880	19328-19458	Sentence	denotes	Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.
TextSentencer_T133	19459-19823	Sentence	denotes	While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .
TextSentencer_T133	19459-19823	Sentence	denotes	While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .
T22103	19459-19823	Sentence	denotes	While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .
TextSentencer_T134	19824-19945	Sentence	denotes	MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.
TextSentencer_T134	19824-19945	Sentence	denotes	MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.
T20259	19824-19945	Sentence	denotes	MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.
TextSentencer_T135	19946-20177	Sentence	denotes	Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .
TextSentencer_T135	19946-20177	Sentence	denotes	Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .
T13519	19946-20177	Sentence	denotes	Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .
TextSentencer_T136	20178-20315	Sentence	denotes	Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).
TextSentencer_T136	20178-20315	Sentence	denotes	Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).
T42464	20178-20315	Sentence	denotes	Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).
TextSentencer_T137	20316-20463	Sentence	denotes	For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:
TextSentencer_T137	20316-20463	Sentence	denotes	For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:
T22111	20316-20463	Sentence	denotes	For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:
TextSentencer_T138	20464-20585	Sentence	denotes	A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .
TextSentencer_T138	20464-20585	Sentence	denotes	A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .
T19987	20464-20585	Sentence	denotes	A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .
TextSentencer_T139	20586-20680	Sentence	denotes	In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.
TextSentencer_T139	20586-20680	Sentence	denotes	In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.
T56270	20586-20680	Sentence	denotes	In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.
TextSentencer_T140	20681-20844	Sentence	denotes	Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.
TextSentencer_T140	20681-20844	Sentence	denotes	Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.
T58549	20681-20844	Sentence	denotes	Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.
TextSentencer_T141	20845-21026	Sentence	denotes	As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.
TextSentencer_T141	20845-21026	Sentence	denotes	As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.
T22452	20845-21026	Sentence	denotes	As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.
TextSentencer_T142	21027-21276	Sentence	denotes	Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .
TextSentencer_T142	21027-21276	Sentence	denotes	Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .
T39728	21027-21276	Sentence	denotes	Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .
TextSentencer_T143	21277-21409	Sentence	denotes	Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.
TextSentencer_T143	21277-21409	Sentence	denotes	Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.
T20011	21277-21409	Sentence	denotes	Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.
TextSentencer_T144	21410-21501	Sentence	denotes	This is advantageous as all samples are processed equally excluding sample handling biases.
TextSentencer_T144	21410-21501	Sentence	denotes	This is advantageous as all samples are processed equally excluding sample handling biases.
T28781	21410-21501	Sentence	denotes	This is advantageous as all samples are processed equally excluding sample handling biases.
TextSentencer_T145	21502-21597	Sentence	denotes	Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.
TextSentencer_T145	21502-21597	Sentence	denotes	Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.
T54018	21502-21597	Sentence	denotes	Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.
TextSentencer_T146	21598-21709	Sentence	denotes	Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.
TextSentencer_T146	21598-21709	Sentence	denotes	Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.
T16361	21598-21709	Sentence	denotes	Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.
TextSentencer_T147	21710-21841	Sentence	denotes	Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.
TextSentencer_T147	21710-21841	Sentence	denotes	Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.
T77066	21710-21841	Sentence	denotes	Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.
TextSentencer_T148	21842-21953	Sentence	denotes	Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.
TextSentencer_T148	21842-21953	Sentence	denotes	Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.
T63761	21842-21953	Sentence	denotes	Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.
TextSentencer_T149	21954-22110	Sentence	denotes	Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .
TextSentencer_T149	21954-22110	Sentence	denotes	Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .
T77827	21954-22110	Sentence	denotes	Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .
TextSentencer_T150	22111-22202	Sentence	denotes	The high accuracy of SILAC typically requires analysis of only two experimental replicates.
TextSentencer_T150	22111-22202	Sentence	denotes	The high accuracy of SILAC typically requires analysis of only two experimental replicates.
T72792	22111-22202	Sentence	denotes	The high accuracy of SILAC typically requires analysis of only two experimental replicates.
TextSentencer_T151	22203-22309	Sentence	denotes	In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.
TextSentencer_T151	22203-22309	Sentence	denotes	In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.
T24098	22203-22309	Sentence	denotes	In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.
TextSentencer_T152	22310-22415	Sentence	denotes	Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.
TextSentencer_T152	22310-22415	Sentence	denotes	Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.
T55917	22310-22415	Sentence	denotes	Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.
TextSentencer_T153	22416-22582	Sentence	denotes	Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).
TextSentencer_T153	22416-22582	Sentence	denotes	Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).
T26826	22416-22582	Sentence	denotes	Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).
TextSentencer_T154	22583-22618	Sentence	denotes	Fig. 3A depicts the SILAC workflow.
TextSentencer_T154	22583-22618	Sentence	denotes	Fig. 3A depicts the SILAC workflow.
T45285	22583-22618	Sentence	denotes	Fig. 3A depicts the SILAC workflow.
TextSentencer_T155	22619-22687	Sentence	denotes	SILAC followed by LC-MS/MS can answer various questions in virology.
TextSentencer_T155	22619-22687	Sentence	denotes	SILAC followed by LC-MS/MS can answer various questions in virology.
T17055	22619-22687	Sentence	denotes	SILAC followed by LC-MS/MS can answer various questions in virology.
TextSentencer_T156	22688-22814	Sentence	denotes	For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .
TextSentencer_T156	22688-22814	Sentence	denotes	For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .
T1662	22688-22814	Sentence	denotes	For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .
TextSentencer_T157	22815-22966	Sentence	denotes	Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .
TextSentencer_T157	22815-22966	Sentence	denotes	Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .
T53415	22815-22966	Sentence	denotes	Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .
TextSentencer_T158	22967-23190	Sentence	denotes	For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .
TextSentencer_T158	22967-23190	Sentence	denotes	For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .
T82133	22967-23190	Sentence	denotes	For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .
TextSentencer_T159	23191-23587	Sentence	denotes	Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .
TextSentencer_T159	23191-23587	Sentence	denotes	Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .
T69945	23191-23587	Sentence	denotes	Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .
TextSentencer_T160	23588-23687	Sentence	denotes	SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.
TextSentencer_T160	23588-23687	Sentence	denotes	SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.
T21335	23588-23687	Sentence	denotes	SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.
TextSentencer_T161	23688-23801	Sentence	denotes	For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .
TextSentencer_T161	23688-23801	Sentence	denotes	For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .
T20070	23688-23801	Sentence	denotes	For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .
TextSentencer_T162	23802-24029	Sentence	denotes	In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).
TextSentencer_T162	23802-24029	Sentence	denotes	In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).
T45508	23802-24029	Sentence	denotes	In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).
TextSentencer_T163	24030-24172	Sentence	denotes	High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.
TextSentencer_T163	24030-24172	Sentence	denotes	High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.
T4723	24030-24172	Sentence	denotes	High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.
TextSentencer_T164	24173-24353	Sentence	denotes	A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .
TextSentencer_T164	24173-24353	Sentence	denotes	A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .
T97054	24173-24353	Sentence	denotes	A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .
TextSentencer_T165	24354-24449	Sentence	denotes	A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.
TextSentencer_T165	24354-24449	Sentence	denotes	A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.
T58147	24354-24449	Sentence	denotes	A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.
TextSentencer_T166	24450-24519	Sentence	denotes	SILAC is applicable to most cell culture cells and sample conditions.
TextSentencer_T166	24450-24519	Sentence	denotes	SILAC is applicable to most cell culture cells and sample conditions.
T11899	24450-24519	Sentence	denotes	SILAC is applicable to most cell culture cells and sample conditions.
TextSentencer_T167	24520-24624	Sentence	denotes	Even SILAC mice have been developed in the past for ex vivo proteomics analyses (Zanivan et al., 2012) .
TextSentencer_T167	24520-24624	Sentence	denotes	Even SILAC mice have been developed in the past for ex vivo proteomics analyses (Zanivan et al., 2012) .

TextSentencer_T1

0-71

Sentence

denotes

Decoding protein networks during virus entry by quantitative proteomics

TextSentencer_T1

0-71

Sentence

denotes

Decoding protein networks during virus entry by quantitative proteomics

T12890

0-71

Sentence

denotes

Decoding protein networks during virus entry by quantitative proteomics

TextSentencer_T2

73-81

Sentence

denotes

Abstract

TextSentencer_T2

73-81

Sentence

denotes

Abstract

T29442

73-81

Sentence

denotes

Abstract

TextSentencer_T3

82-212

Sentence

denotes

Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.

TextSentencer_T3

82-212

Sentence

denotes

Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.

T53843

82-212

Sentence

denotes

Virus entry into host cells relies on interactions between viral and host structures including lipids, carbohydrates and proteins.

TextSentencer_T4

213-421

Sentence

denotes

Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.

TextSentencer_T4

213-421

Sentence

denotes

Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.

T9946

213-421

Sentence

denotes

Particularly, protein-protein interactions between viral surface proteins and host proteins as well as secondary host protein-protein interactions play a pivotal role in coordinating virus binding and uptake.

TextSentencer_T5

422-499

Sentence

denotes

These interactions are dynamic and frequently involve multiprotein complexes.

TextSentencer_T5

422-499

Sentence

denotes

These interactions are dynamic and frequently involve multiprotein complexes.

T29142

422-499

Sentence

denotes

These interactions are dynamic and frequently involve multiprotein complexes.

TextSentencer_T6

500-738

Sentence

denotes

In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.

TextSentencer_T6

500-738

Sentence

denotes

In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.

T16324

500-738

Sentence

denotes

In the past decade mass spectrometry based proteomics methods have reached sensitivities and high throughput compatibilities of genomics methods and now allow the reliable quantitation of proteins in complex samples from limited material.

TextSentencer_T7

739-984

Sentence

denotes

As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.

TextSentencer_T7

739-984

Sentence

denotes

As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.

T20689

739-984

Sentence

denotes

As proteomics provides essential information on the biologically active entity namely the protein, including its posttranslational modifications and its interactions with other proteins, it is an indispensable method in the virologist's toolbox.

TextSentencer_T8

985-1164

Sentence

denotes

Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.

TextSentencer_T8

985-1164

Sentence

denotes

Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.

T41706

985-1164

Sentence

denotes

Here we review protein interactions during virus entry and compare classical biochemical methods to study entry with novel technically advanced quantitative proteomics techniques.

TextSentencer_T9

1165-1407

Sentence

denotes

We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.

TextSentencer_T9

1165-1407

Sentence

denotes

We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.

T62877

1165-1407

Sentence

denotes

We highlight the value of quantitative proteomics in mapping functional virus entry networks, discuss the benefits and limitations and illustrate how the methodology will help resolve unsettled questions in virus entry research in the future.

TextSentencer_T10

1409-1486

Sentence

denotes

Viruses need to enter permissive host cells in order to propagate and spread.

TextSentencer_T10

1409-1486

Sentence

denotes

Viruses need to enter permissive host cells in order to propagate and spread.

T99277

1409-1486

Sentence

denotes

Viruses need to enter permissive host cells in order to propagate and spread.

TextSentencer_T11

1487-1581

Sentence

denotes

The penetration of cells requires an initial interaction of viral and host surface structures.

TextSentencer_T11

1487-1581

Sentence

denotes

The penetration of cells requires an initial interaction of viral and host surface structures.

T5874

1487-1581

Sentence

denotes

The penetration of cells requires an initial interaction of viral and host surface structures.

TextSentencer_T12

1582-1713

Sentence

denotes

Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.

TextSentencer_T12

1582-1713

Sentence

denotes

Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.

T28063

1582-1713

Sentence

denotes

Typical viral attachment proteins (VAP) are transmembrane glycoproteins for enveloped viruses or capsid proteins for naked viruses.

TextSentencer_T13

1714-1992

Sentence

denotes

Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .

TextSentencer_T13

1714-1992

Sentence

denotes

Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .

T8637

1714-1992

Sentence

denotes

Alternatively, some viruses incorporate phosphatidylserine into their envelope and use this lipid for host cell interaction (Amara and Mercer, 2015; Jemielity et al., 2013; Kondratowicz et al., 2011; Mercer and Helenius, 2008; Moller-Tank et al., 2013; Shimojima et al., 2012) .

TextSentencer_T14

1993-2204

Sentence

denotes

For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.

TextSentencer_T14

1993-2204

Sentence

denotes

For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.

T40365

1993-2204

Sentence

denotes

For the majority of viruses, however, proteins bind to cellular receptors, i.e., proteins or carbohydrates, and the expression of a particular receptor is often determining tissue and species tropism of a virus.

TextSentencer_T15

2205-2494

Sentence

denotes

In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .

TextSentencer_T15

2205-2494

Sentence

denotes

In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .

T83209

2205-2494

Sentence

denotes

In this review we focus on the role of protein-protein interactions (PPI) during viral penetration as protein-lipid and protein-carbohydrate interactions in cell entry of viruses have been discussed elsewhere (Amara and Mercer, 2015; Lozach et al., 2007; Stencel-Baerenwald et al., 2014) .

TextSentencer_T16

2495-2553

Sentence

denotes

Historically, the first virus receptor found was a glycan.

TextSentencer_T16

2495-2553

Sentence

denotes

Historically, the first virus receptor found was a glycan.

T68800

2495-2553

Sentence

denotes

Historically, the first virus receptor found was a glycan.

TextSentencer_T17

2554-2664

Sentence

denotes

In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .

TextSentencer_T17

2554-2664

Sentence

denotes

In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .

T32807

2554-2664

Sentence

denotes

In 1981 Helenius and coworkers described sialic acid as the influenza A virus receptor (Matlin et al., 1981) .

TextSentencer_T18

2665-2798

Sentence

denotes

In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.

TextSentencer_T18

2665-2798

Sentence

denotes

In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.

T37788

2665-2798

Sentence

denotes

In the following years it became clear that most virus receptors are proteins or protein-linked entities, such as glycosaminoglycans.

TextSentencer_T19

2799-2901

Sentence

denotes

As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.

TextSentencer_T19

2799-2901

Sentence

denotes

As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.

T67553

2799-2901

Sentence

denotes

As a consequence, protease treatment rendered susceptible host cells non-susceptible for many viruses.

TextSentencer_T20

2902-3102

Sentence

denotes

With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .

TextSentencer_T20

2902-3102

Sentence

denotes

With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .

T52334

2902-3102

Sentence

denotes

With the discovery of CR2 as Epstein Barr virus (EBV) and CD4 as human immunodeficiency virus type 1 (HIV-1) receptor the hunt for virus receptors began (Fingeroth et al., 1984; Maddon et al., 1986) .

TextSentencer_T21

3103-3358

Sentence

denotes

Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .

TextSentencer_T21

3103-3358

Sentence

denotes

Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .

T65342

3103-3358

Sentence

denotes

Since then technological developments like antibody based affinity purification (AP), mass spectrometry (MS) of proteins, DNA mediated transformation and molecular cloning led to the discovery of dozens of receptors for human pathogenic viruses (Fig. 1) .

TextSentencer_T22

3359-3506

Sentence

denotes

Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.

TextSentencer_T22

3359-3506

Sentence

denotes

Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.

T99710

3359-3506

Sentence

denotes

Nevertheless, for many viruses the cognate receptor(s) remain enigmatic and a "one fits all" method for their discovery has not yet been described.

TextSentencer_T23

3507-3629

Sentence

denotes

Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.

TextSentencer_T23

3507-3629

Sentence

denotes

Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.

T69360

3507-3629

Sentence

denotes

Virus entry factors, which interact with VAPs directly, can be differentiated into attachment factors and entry receptors.

TextSentencer_T24

3630-3646

Sentence

denotes

Attach- surface.

TextSentencer_T24

3630-3646

Sentence

denotes

Attach- surface.

T50255

3630-3646

Sentence

denotes

Attach- surface.

TextSentencer_T25

3647-3805

Sentence

denotes

Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).

TextSentencer_T25

3647-3805

Sentence

denotes

Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).

T78720

3647-3805

Sentence

denotes

Virus receptors not only mediate cell attachment but the PPI of VAP and receptor also guides subsequent entry steps, e.g. internalization ( Fig. 2 and Box 1).

TextSentencer_T26

3806-3959

Sentence

denotes

Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.

TextSentencer_T26

3806-3959

Sentence

denotes

Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.

T41393

3806-3959

Sentence

denotes

Sometimes the VAP-receptor interaction unleashes the fusogenic property of viral glycoproteins by inducing conformational changes in the VAP ectodomains.

TextSentencer_T27

3960-4089

Sentence

denotes

A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .

TextSentencer_T27

3960-4089

Sentence

denotes

A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .

T14668

3960-4089

Sentence

denotes

A well-studied example is the priming of the hepatitis C virus (HCV) glycoprotein E2 by the CD81 receptor (Sharma et al., 2011) .

TextSentencer_T28

4090-4204

Sentence

denotes

For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.

TextSentencer_T28

4090-4204

Sentence

denotes

For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.

T76750

4090-4204

Sentence

denotes

For viruses, which fuse in intracellular vesicular compartments, a drop in pH typically acts as primer for fusion.

TextSentencer_T29

4205-4289

Sentence

denotes

In some cases host proteases interact with and cleave VAPs rendering them fusogenic.

TextSentencer_T29

4205-4289

Sentence

denotes

In some cases host proteases interact with and cleave VAPs rendering them fusogenic.

T53591

4205-4289

Sentence

denotes

In some cases host proteases interact with and cleave VAPs rendering them fusogenic.

TextSentencer_T30

4290-4394

Sentence

denotes

PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.

TextSentencer_T30

4290-4394

Sentence

denotes

PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.

T19124

4290-4394

Sentence

denotes

PPIs between viral and cellular factors orchestrate viral attachment, trafficking, fusion and uncoating.

TextSentencer_T31

4395-4476

Sentence

denotes

Classical virus infection pathways are illustrated for a generic enveloped virus.

TextSentencer_T31

4395-4476

Sentence

denotes

Classical virus infection pathways are illustrated for a generic enveloped virus.

T38807

4395-4476

Sentence

denotes

Classical virus infection pathways are illustrated for a generic enveloped virus.

TextSentencer_T32

4477-4620

Sentence

denotes

Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).

TextSentencer_T32

4477-4620

Sentence

denotes

Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).

T22370

4477-4620

Sentence

denotes

Note that naked virions infect cells in a similar manner with viral capsid proteins mediating critical PPIs with cellular proteins (not shown).

TextSentencer_T33

4621-4700

Sentence

denotes

PPIs facilitating virus attachment, surfing, fusion and transport are depicted.

TextSentencer_T33

4621-4700

Sentence

denotes

PPIs facilitating virus attachment, surfing, fusion and transport are depicted.

T35485

4621-4700

Sentence

denotes

PPIs facilitating virus attachment, surfing, fusion and transport are depicted.

TextSentencer_T34

4701-4794

Sentence

denotes

In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.

TextSentencer_T34

4701-4794

Sentence

denotes

In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.

T81601

4701-4794

Sentence

denotes

In some cases proteolytic processing mediated by host factors triggers viral membrane fusion.

TextSentencer_T35

4795-4934

Sentence

denotes

Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.

TextSentencer_T35

4795-4934

Sentence

denotes

Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.

T91634

4795-4934

Sentence

denotes

Moreover, secondary PPIs can lead to assembly of multiprotein receptor platforms that allow internalization and ultimately membrane fusion.

TextSentencer_T36

4935-5026

Sentence

denotes

Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.

TextSentencer_T36

4935-5026

Sentence

denotes

Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.

T88841

4935-5026

Sentence

denotes

Proteolytic processing of VAPs either occurs during VAP biosynthesis or during virus entry.

TextSentencer_T37

5027-5169

Sentence

denotes

The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .

TextSentencer_T37

5027-5169

Sentence

denotes

The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .

T82857

5027-5169

Sentence

denotes

The latter applies to ebola virus, which requires processing of its envelope glycoprotein by cathepsins in endosomes (Chandran et al., 2005) .

TextSentencer_T38

5170-5355

Sentence

denotes

Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .

TextSentencer_T38

5170-5355

Sentence

denotes

Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .

T86845

5170-5355

Sentence

denotes

Moreover, interactions of VAPs with secondary receptors, occurring after membrane surfing of viruses towards cellular junctions may trigger internalization (Coyne and Bergelson, 2006) .

TextSentencer_T39

5356-5526

Sentence

denotes

After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .

TextSentencer_T39

5356-5526

Sentence

denotes

After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .

T29961

5356-5526

Sentence

denotes

After endocytosis, secondary PPIs with endosomal receptors can in addition to the pH drop render viral glycoproteins fusogenic (Carette et al., 2011; Cote et al., 2011) .

TextSentencer_T40

5527-5686

Sentence

denotes

Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.

TextSentencer_T40

5527-5686

Sentence

denotes

Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.

T78499

5527-5686

Sentence

denotes

Subsequently viruses replicating in the nucleus are transported along the cytoskeleton towards the nuclear pore, where the genome is released into the nucleus.

TextSentencer_T41

5687-5778

Sentence

denotes

Transport relies again on PPI of virus structural proteins and microtubular motor proteins.

TextSentencer_T41

5687-5778

Sentence

denotes

Transport relies again on PPI of virus structural proteins and microtubular motor proteins.

T14100

5687-5778

Sentence

denotes

Transport relies again on PPI of virus structural proteins and microtubular motor proteins.

TextSentencer_T42

5779-5917

Sentence

denotes

All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.

TextSentencer_T42

5779-5917

Sentence

denotes

All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.

T79897

5779-5917

Sentence

denotes

All viruses additionally need to undergo uncoating, i.e., the viral nucleocapsid needs to disassemble to release the genome into the cell.

TextSentencer_T43

5918-6052

Sentence

denotes

Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.

TextSentencer_T43

5918-6052

Sentence

denotes

Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.

T72564

5918-6052

Sentence

denotes

Uncoating is poorly understood for most viruses, but as detailed below, also requires interaction of viral capsids with host proteins.

TextSentencer_T44

6053-6142

Sentence

denotes

Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.

TextSentencer_T44

6053-6142

Sentence

denotes

Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.

T89371

6053-6142

Sentence

denotes

Fig. 2 highlights the most important steps in virus entry and critical PPI for each step.

TextSentencer_T45

6143-6211

Sentence

denotes

In brief, most processes during virus entry are coordinated by PPIs.

TextSentencer_T45

6143-6211

Sentence

denotes

In brief, most processes during virus entry are coordinated by PPIs.

T96058

6143-6211

Sentence

denotes

In brief, most processes during virus entry are coordinated by PPIs.

TextSentencer_T46

6212-6376

Sentence

denotes

In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.

TextSentencer_T46

6212-6376

Sentence

denotes

In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.

T72320

6212-6376

Sentence

denotes

In fact, eighty percent of the approximately 20,000 protein coding genes of a cell are estimated to perform their function through interactions with other proteins.

TextSentencer_T47

6377-6601

Sentence

denotes

Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .

TextSentencer_T47

6377-6601

Sentence

denotes

Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .

T18904

6377-6601

Sentence

denotes

Roughly 10,000 distinct interaction types, i.e., structurally similar interactions, and 130,000-650,000 binary protein interactions can occur in a cell (Aloy and Russell, 2004; Stumpf et al., 2008; Venkatesan et al., 2009) .

TextSentencer_T48

6602-6757

Sentence

denotes

Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.

TextSentencer_T48

6602-6757

Sentence

denotes

Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.

T93501

6602-6757

Sentence

denotes

Thus, knowledge on protein complexes is essential for the understanding of cellular mechanisms and for the targeted interference with a protein's function.

TextSentencer_T49

6758-6886

Sentence

denotes

In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.

TextSentencer_T49

6758-6886

Sentence

denotes

In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.

T543

6758-6886

Sentence

denotes

In some instances this knowledge has been successfully translated into therapeutic approaches for treatment of viral infections.

TextSentencer_T50

6887-7039

Sentence

denotes

The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .

TextSentencer_T50

6887-7039

Sentence

denotes

The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .

T84284

6887-7039

Sentence

denotes

The best known examples are the HIV-1 CCR5 coreceptor antagonist maraviroc and the HIV-1 gp41 fusion inhibitors (Dorr et al., 2005; Wild et al., 1993) .

TextSentencer_T51

7040-7189

Sentence

denotes

Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.

TextSentencer_T51

7040-7189

Sentence

denotes

Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.

T464

7040-7189

Sentence

denotes

Importantly, many interactions are mediated by short 10 amino acid long unstructured peptide motifs, are transient, and have relatively low affinity.

TextSentencer_T52

7190-7295

Sentence

denotes

Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.

TextSentencer_T52

7190-7295

Sentence

denotes

Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.

T49143

7190-7295

Sentence

denotes

Classical high stringency tandem AP protocols thus often missed peptide motif based protein interactions.

TextSentencer_T53

7296-7445

Sentence

denotes

Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.

TextSentencer_T53

7296-7445

Sentence

denotes

Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.

T94739

7296-7445

Sentence

denotes

Novel shotgun proteomics of one step affinity enriched samples provides now the opportunity to unravel a multitude of previously missed interactions.

TextSentencer_T54

7446-7758

Sentence

denotes

Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:

TextSentencer_T54

7446-7758

Sentence

denotes

Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:

T77542

7446-7758

Sentence

denotes

Typical host peptide motifs, which coordinate PPIs and occur in several hundred human proteins, are the functional unit of src-homology 2 domain (SH2-domain), SH3-domain, the post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1)-domain Box 1:

TextSentencer_T55

7759-7804

Sentence

denotes

Definitions and abbreviations in virus entry.

TextSentencer_T55

7759-7804

Sentence

denotes

Definitions and abbreviations in virus entry.

T54192

7759-7804

Sentence

denotes

Definitions and abbreviations in virus entry.

TextSentencer_T56

7805-7910

Sentence

denotes

Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.

TextSentencer_T56

7805-7910

Sentence

denotes

Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.

T49236

7805-7910

Sentence

denotes

Susceptible cell: cell that expresses virus receptors and entry factors and thus allows entry of a virus.

TextSentencer_T57

7911-8080

Sentence

denotes

Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.

TextSentencer_T57

7911-8080

Sentence

denotes

Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.

T64260

7911-8080

Sentence

denotes

Permissive cell: cell that expresses all host factors required for replication, assembly and release of a virus and thus can generate infectious progeny after infection.

TextSentencer_T58

8081-8184

Sentence

denotes

Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.

TextSentencer_T58

8081-8184

Sentence

denotes

Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.

T23061

8081-8184

Sentence

denotes

Virus entry: process of delivery of the viral genome to the viral replication compartment in the cells.

TextSentencer_T59

8185-8437

Sentence

denotes

Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.

TextSentencer_T59

8185-8437

Sentence

denotes

Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.

T81179

8185-8437

Sentence

denotes

Depending on the replication site and the virus entry route, virus entry includes cell attachment, endocytosis, membrane penetration, trafficking in the cytoplasm, nuclear import, release of viral structural proteins like tegument and genome uncoating.

TextSentencer_T60

8438-8509

Sentence

denotes

Virus attachment factor: cell surface protein interacting with a virus.

TextSentencer_T60

8438-8509

Sentence

denotes

Virus attachment factor: cell surface protein interacting with a virus.

T29981

8438-8509

Sentence

denotes

Virus attachment factor: cell surface protein interacting with a virus.

TextSentencer_T61

8510-8652

Sentence

denotes

Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.

TextSentencer_T61

8510-8652

Sentence

denotes

Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.

T14346

8510-8652

Sentence

denotes

Attachment factors facilitate entry by concentrating virions at the cell surface and can promote subsequent interactions with entry receptors.

TextSentencer_T62

8653-8835

Sentence

denotes

Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.

TextSentencer_T62

8653-8835

Sentence

denotes

Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.

T918

8653-8835

Sentence

denotes

Virus entry receptor: cellular protein, lipid or glycan that binds the virus particle and mediates virus uptake and/or triggers critical conformational changes crucial for infection.

TextSentencer_T63

8836-8942

Sentence

denotes

Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.

TextSentencer_T63

8836-8942

Sentence

denotes

Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.

T17841

8836-8942

Sentence

denotes

Viral receptors are often localized to the plasma membrane, but can also reside in endosomal compartments.

TextSentencer_T64

8943-9111

Sentence

denotes

Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.

TextSentencer_T64

8943-9111

Sentence

denotes

Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.

T66051

8943-9111

Sentence

denotes

Virus entry factor: operationally defined as any cellular factor that in some way participates in the virus entry process, but not necessarily interacts with the virus.

TextSentencer_T65

9112-9199

Sentence

denotes

Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.

TextSentencer_T65

9112-9199

Sentence

denotes

Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.

T4399

9112-9199

Sentence

denotes

Viral attachment protein (VAP): viral surface protein that binds to the virus receptor.

TextSentencer_T66

9200-9313

Sentence

denotes

VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.

TextSentencer_T66

9200-9313

Sentence

denotes

VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.

T19538

9200-9313

Sentence

denotes

VAPs of enveloped viruses are transmembrane glycoproteins, while VAPs of naked viruses are viral capsid proteins.

TextSentencer_T67

9314-9327

Sentence

denotes

Capsid (also:

TextSentencer_T67

9314-9327

Sentence

denotes

Capsid (also:

T10656

9314-9327

Sentence

denotes

Capsid (also:

TextSentencer_T68

9328-9475

Sentence

denotes

Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.

TextSentencer_T68

9328-9475

Sentence

denotes

Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.

T98319

9328-9475

Sentence

denotes

Core): protein shell of a virus arranged around the viral genome or complexed to it; build by repeat units of single proteins or protein complexes.

TextSentencer_T69

9476-9528

Sentence

denotes

The capsid proteins are encoded by the viral genome.

TextSentencer_T69

9476-9528

Sentence

denotes

The capsid proteins are encoded by the viral genome.

T91521

9476-9528

Sentence

denotes

The capsid proteins are encoded by the viral genome.

TextSentencer_T70

9529-9644

Sentence

denotes

Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.

TextSentencer_T70

9529-9644

Sentence

denotes

Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.

T17928

9529-9644

Sentence

denotes

Nucleocapsid: complex of viral genome and capsid, which may for enveloped viruses be surrounded by a lipid bilayer.

TextSentencer_T71

9645-9660

Sentence

denotes

Envelope (also:

TextSentencer_T71

9645-9660

Sentence

denotes

Envelope (also:

T20410

9645-9660

Sentence

denotes

Envelope (also:

TextSentencer_T72

9661-9752

Sentence

denotes

Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.

TextSentencer_T72

9661-9752

Sentence

denotes

Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.

T76425

9661-9752

Sentence

denotes

Peplos): host cell derived lipid bilayer surrounding the nucleocapsid of enveloped viruses.

TextSentencer_T73

9753-9829

Sentence

denotes

The envelope typically displays viral genome encoded transmembrane proteins.

TextSentencer_T73

9753-9829

Sentence

denotes

The envelope typically displays viral genome encoded transmembrane proteins.

T80675

9753-9829

Sentence

denotes

The envelope typically displays viral genome encoded transmembrane proteins.

TextSentencer_T74

9830-10021

Sentence

denotes

These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.

TextSentencer_T74

9830-10021

Sentence

denotes

These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.

T78007

9830-10021

Sentence

denotes

These envelope proteins are VAPs and in some cases enzymes (neuraminidases) that cleave cellular carbohydrates to facilitate virus shedding or ion channel proteins that prime viral uncoating.

TextSentencer_T75

10022-10131

Sentence

denotes

Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.

TextSentencer_T75

10022-10131

Sentence

denotes

Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.

T69661

10022-10131

Sentence

denotes

Recently, it was shown that some classical naked viruses, like hepatitis A virus, could be enveloped as well.

TextSentencer_T76

10132-10534

Sentence

denotes

Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.

TextSentencer_T76

10132-10534

Sentence

denotes

Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.

T57340

10132-10534

Sentence

denotes

Virion surfing: directional movement of virions within the cell plasma membrane, i.e. on the cell surface or cell projections like filipodia, towards the viral entry sites Virus fusion: membrane mixing of the lipid bilayer of enveloped viruses with a host cell lipid bilayer, i.e. either the plasma membrane or the endosomal membrane, resulting in the release of viral nucleocapsids into the cytoplasm.

TextSentencer_T77

10535-10649

Sentence

denotes

Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.

TextSentencer_T77

10535-10649

Sentence

denotes

Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.

T98257

10535-10649

Sentence

denotes

Uncoating: disassembly of the viral capsid to release the viral genome into the cytosol or nucleus of a host cell.

TextSentencer_T78

10650-10745

Sentence

denotes

Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.

TextSentencer_T78

10650-10745

Sentence

denotes

Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.

T33551

10650-10745

Sentence

denotes

Large DNA viruses additionally require tegument disassembly prior to disassembly of the capsid.

TextSentencer_T79

10746-10859

Sentence

denotes

(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .

TextSentencer_T79

10746-10859

Sentence

denotes

(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .

T73798

10746-10859

Sentence

denotes

(PDZ-domain) and the so called WW-domains which carry two tryptophan residues as signature (Tompa et al., 2014) .

TextSentencer_T80

10860-11041

Sentence

denotes

Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .

TextSentencer_T80

10860-11041

Sentence

denotes

Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .

T98929

10860-11041

Sentence

denotes

Notably, viruses and other pathogens often make use of these and other peptide motifs to hijack cellular pathways during their life cycle including virus entry Hagai et al., 2014) .

TextSentencer_T81

11042-11295

Sentence

denotes

While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).

TextSentencer_T81

11042-11295

Sentence

denotes

While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).

T50256

11042-11295

Sentence

denotes

While transcriptomics can reveal long-term alterations of the cellular state, virus entry usually occurs within minutes and typically relies on rapid changes of protein conformation, localization, interactions and post-translational modifications (PTM).

TextSentencer_T82

11296-11438

Sentence

denotes

Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.

TextSentencer_T82

11296-11438

Sentence

denotes

Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.

T47922

11296-11438

Sentence

denotes

Thus studying the proteome state, preferentially in a time-resolved manner, is ideally suited for understanding the mechanisms of virus entry.

TextSentencer_T83

11439-11548

Sentence

denotes

Proteomics has already led to the characterization of global cellular alterations induced by virus infection.

TextSentencer_T83

11439-11548

Sentence

denotes

Proteomics has already led to the characterization of global cellular alterations induced by virus infection.

T74571

11439-11548

Sentence

denotes

Proteomics has already led to the characterization of global cellular alterations induced by virus infection.

TextSentencer_T84

11549-11808

Sentence

denotes

For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .

TextSentencer_T84

11549-11808

Sentence

denotes

For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .

T43139

11549-11808

Sentence

denotes

For instance, virus induced changes in the protein composition of subcellular HCV replication compartments revealed several host replication and assembly factors (Huang et al., 2007; Mannova et al., 2006; Paul et al., 2013; Yi et al., 2006; Yi et al., 2011) .

TextSentencer_T85

11809-12026

Sentence

denotes

Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .

TextSentencer_T85

11809-12026

Sentence

denotes

Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .

T44392

11809-12026

Sentence

denotes

Interaction proteomics at a large scale was moreover performed for all 18 HIV-1 proteins outside of the context of HIV-1 infection and revealed important virus manipulations of cellular pathways (Jager et al., 2012) .

TextSentencer_T86

12027-12211

Sentence

denotes

Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .

TextSentencer_T86

12027-12211

Sentence

denotes

Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .

T49837

12027-12211

Sentence

denotes

Another global interaction proteomics study revealed host protein interactions of viral immune modulating proteins uncovering viral immune evasion strategies (Pichlmair et al., 2012) .

TextSentencer_T87

12212-12345

Sentence

denotes

Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.

TextSentencer_T87

12212-12345

Sentence

denotes

Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.

T72696

12212-12345

Sentence

denotes

Although in principle possible, global interaction proteomics during virus attachment and entry has not yet been extensively pursued.

TextSentencer_T88

12346-12568

Sentence

denotes

As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.

TextSentencer_T88

12346-12568

Sentence

denotes

As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.

T30361

12346-12568

Sentence

denotes

As virus entry is the process in the viral life cycle, which can most easily be synchronized by inhibitors or temperature shifts, we believe that proteomic analyses can close many gaps of knowledge in virus entry research.

TextSentencer_T89

12569-12685

Sentence

denotes

Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.

TextSentencer_T89

12569-12685

Sentence

denotes

Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.

T71706

12569-12685

Sentence

denotes

Below we discuss successful applications of proteomics to understand virus uptake and highlight future perspectives.

TextSentencer_T90

12686-12823

Sentence

denotes

The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .

TextSentencer_T90

12686-12823

Sentence

denotes

The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .

T70815

12686-12823

Sentence

denotes

The various entry routes of viruses have been extensively reviewed (Grove and Marsh, 2011; Mercer et al., 2010; Amara and Mercer, 2015) .

TextSentencer_T91

12824-13139

Sentence

denotes

Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .

TextSentencer_T91

12824-13139

Sentence

denotes

Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .

T35308

12824-13139

Sentence

denotes

Similarly, we refer the reader elsewhere for methods to define protein interactions other than MS based proteomics, i.e., native PAGE, yeast two hybrid, protein microarrays, fluorescence resonance energy transfer, surface plasmon resonance, structurebased approaches and phage display (Ngounou Wetie et al., 2014) .

TextSentencer_T92

13140-13281

Sentence

denotes

Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.

TextSentencer_T92

13140-13281

Sentence

denotes

Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.

T24661

13140-13281

Sentence

denotes

Here, we focus on the PPIs and PTMs that mediate virus uptake and on past and present MS proteomics based techniques to study virus invasion.

TextSentencer_T93

13282-13412

Sentence

denotes

To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.

TextSentencer_T93

13282-13412

Sentence

denotes

To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.

T40962

13282-13412

Sentence

denotes

To gain access to a susceptible host cell the vast majority of viruses interacts with proteinacious receptors on the cell surface.

TextSentencer_T94

13413-13527

Sentence

denotes

Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .

TextSentencer_T94

13413-13527

Sentence

denotes

Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .

T72578

13413-13527

Sentence

denotes

Consequently, biochemical protein-based approaches successfully discovered virus receptors in the past (Table 1) .

TextSentencer_T95

13528-13607

Sentence

denotes

Typically, these approaches build on virus overlay protein blot assays (VOPBA).

TextSentencer_T95

13528-13607

Sentence

denotes

Typically, these approaches build on virus overlay protein blot assays (VOPBA).

T2414

13528-13607

Sentence

denotes

Typically, these approaches build on virus overlay protein blot assays (VOPBA).

TextSentencer_T96

13608-13798

Sentence

denotes

VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .

TextSentencer_T96

13608-13798

Sentence

denotes

VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .

T5005

13608-13798

Sentence

denotes

VOPBA relies on probing of cell lysates or cell membrane extracts, separated by gel electrophoresis and transferred onto nitrocellulose membranes, with virus particles (Boyle et al., 1987) .

TextSentencer_T97

13799-13942

Sentence

denotes

Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.

TextSentencer_T97

13799-13942

Sentence

denotes

Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.

T25251

13799-13942

Sentence

denotes

Virus bound proteins are in this case either detected by radiolabelling of the virus or by specific antibodies against the virus glycoproteins.

TextSentencer_T98

13943-14051

Sentence

denotes

In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.

TextSentencer_T98

13943-14051

Sentence

denotes

In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.

T15434

13943-14051

Sentence

denotes

In both cases MS fingerprinting of a corresponding polyacrylamide gel band identifies the putative receptor.

TextSentencer_T99

14052-14203

Sentence

denotes

A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .

TextSentencer_T99

14052-14203

Sentence

denotes

A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .

T28498

14052-14203

Sentence

denotes

A prime example for VOPBA approaches is the identification of alpha-dystroglycan as receptor for lymphocytic choriomenigitis virus (Cao et al., 1998) .

TextSentencer_T100

14204-14447

Sentence

denotes

The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.

TextSentencer_T100

14204-14447

Sentence

denotes

The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.

T76892

14204-14447

Sentence

denotes

The VOPBA qualitative proteomics approach has the advantage that the protein is left intact until the last step of identification and thus information on the molecular weight and posttranslational modifications like glycosylation is available.

TextSentencer_T101

14448-14569

Sentence

denotes

However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.

TextSentencer_T101

14448-14569

Sentence

denotes

However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.

T11811

14448-14569

Sentence

denotes

However, it suffers from low sensitivity, as retrieval of proteins or peptides from polyacrylamide gels is typically low.

TextSentencer_T102

14570-14634

Sentence

denotes

Moreover interactions could be lost under denaturing conditions.

TextSentencer_T102

14570-14634

Sentence

denotes

Moreover interactions could be lost under denaturing conditions.

T5119

14570-14634

Sentence

denotes

Moreover interactions could be lost under denaturing conditions.

TextSentencer_T103

14635-14765

Sentence

denotes

An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.

TextSentencer_T103

14635-14765

Sentence

denotes

An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.

T16806

14635-14765

Sentence

denotes

An alternative to VOPBA-based receptor identification is the affinity purification (AP) of virus glycoprotein -receptor complexes.

TextSentencer_T104

14766-14871

Sentence

denotes

This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.

TextSentencer_T104

14766-14871

Sentence

denotes

This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.

T13318

14766-14871

Sentence

denotes

This method overcomes the caveat of protein denaturation and analyzes interactions in their native state.

TextSentencer_T105

14872-15066

Sentence

denotes

For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .

TextSentencer_T105

14872-15066

Sentence

denotes

For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .

T89440

14872-15066

Sentence

denotes

For instance, Igfusion proteins of truncated soluble viral glycoproteins were successfully used to co-purify the New World arenavirus receptor transferrin receptor 1 (Radoshitzky et al., 2007) .

TextSentencer_T106

15067-15306

Sentence

denotes

Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .

TextSentencer_T106

15067-15306

Sentence

denotes

Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .

T21662

15067-15306

Sentence

denotes

Other examples for qualitative interaction proteomics are the identification of receptors for Nipah virus (ephrin B2), KSHV (ephrin A2) and SARS (angiotensin-converting enzyme 2) (Hahn et al., 2012; Li et al., 2003; Negrete et al., 2005) .

TextSentencer_T107

15307-15400

Sentence

denotes

Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.

TextSentencer_T107

15307-15400

Sentence

denotes

Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.

T15154

15307-15400

Sentence

denotes

Here, glycoprotein−Fc fusion proteins served as baits for AP of the receptor post cell lysis.

TextSentencer_T108

15401-15432

Sentence

denotes

In a third (Yan et al., 2012) .

TextSentencer_T108

15401-15432

Sentence

denotes

In a third (Yan et al., 2012) .

T68869

15401-15432

Sentence

denotes

In a third (Yan et al., 2012) .

TextSentencer_T109

15433-15652

Sentence

denotes

Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.

TextSentencer_T109

15433-15652

Sentence

denotes

Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.

T69534

15433-15652

Sentence

denotes

Generally, biotinylation of surface proteins prior to AP or amine-reactive crosslinking are strategies to increase specificity of the AP and help avoid detection of biologically irrelevant interactions after cell lysis.

TextSentencer_T110

15653-15798

Sentence

denotes

A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.

TextSentencer_T110

15653-15798

Sentence

denotes

A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.

T82467

15653-15798

Sentence

denotes

A refinement of both methods is the use of biotinylated ligands equipped with hydrazine groups for crosslinking of cell surface proteins glycans.

TextSentencer_T111

15799-15921

Sentence

denotes

To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .

TextSentencer_T111

15799-15921

Sentence

denotes

To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .

T27313

15799-15921

Sentence

denotes

To this end, a trifunctional reagent for ligand derivatization, termed TRICEPS, has been developed by Frei et al. (2012) .

TextSentencer_T112

15922-16110

Sentence

denotes

Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.

TextSentencer_T112

15922-16110

Sentence

denotes

Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.

T91687

15922-16110

Sentence

denotes

Critical negative controls further include, non-susceptible cell lines, which do not bind the virus, and glycoprotein mutants or peptide variants, which are deficient for receptor binding.

TextSentencer_T113

16111-16231

Sentence

denotes

In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.

TextSentencer_T113

16111-16231

Sentence

denotes

In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.

T42613

16111-16231

Sentence

denotes

In principle, MS fingerprinting of the purified proteins is the sole method to unambiguously identify the prey after AP.

TextSentencer_T114

16232-16481

Sentence

denotes

It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.

TextSentencer_T114

16232-16481

Sentence

denotes

It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.

T21951

16232-16481

Sentence

denotes

It should however be noted that analysis of the prey with respect to its sensitivity to glycosidases, proteases, heparinases and lipid raft altering agents can lead to an educated guess, which upon further validation might identify a virus receptor.

TextSentencer_T115

16482-16595

Sentence

denotes

A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .

TextSentencer_T115

16482-16595

Sentence

denotes

A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .

T64825

16482-16595

Sentence

denotes

A prominent example is the identification of scavenger receptor class B type I for HCV (Scarselli et al., 2002) .

TextSentencer_T116

16596-16811

Sentence

denotes

Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.

TextSentencer_T116

16596-16811

Sentence

denotes

Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.

T20993

16596-16811

Sentence

denotes

Similar to VOPBA approaches, receptor identification after AP relied on qualitative proteomics in the past, i.e. gel purification of the co-precipitated proteins, followed by MS fingerprinting of a defined gel band.

TextSentencer_T117

16812-16980

Sentence

denotes

Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.

TextSentencer_T117

16812-16980

Sentence

denotes

Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.

T74575

16812-16980

Sentence

denotes

Such interaction proteomics approaches typically require a truncated and epitope tagged virus glycoprotein for efficient affinity enrichment (AE) of cellular receptors.

TextSentencer_T118

16981-17079

Sentence

denotes

High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.

TextSentencer_T118

16981-17079

Sentence

denotes

High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.

T47262

16981-17079

Sentence

denotes

High affinity antibodies against the viral glycoprotein may supersede epitope tagging of the bait.

TextSentencer_T119

17080-17205

Sentence

denotes

Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.

TextSentencer_T119

17080-17205

Sentence

denotes

Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.

T81715

17080-17205

Sentence

denotes

Both VOPBA-based and AP-based interaction proteomics are well suited for the identification of primary receptor interactions.

TextSentencer_T120

17206-17394

Sentence

denotes

However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.

TextSentencer_T120

17206-17394

Sentence

denotes

However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.

T49783

17206-17394

Sentence

denotes

However, interactions with late receptors, which require a conformational change of the glycoprotein and are more difficult to synchronize, cannot be captured easily with these techniques.

TextSentencer_T121

17395-17475

Sentence

denotes

Also virus-triggered secondary PPIs are not resolved by these classical methods.

TextSentencer_T121

17395-17475

Sentence

denotes

Also virus-triggered secondary PPIs are not resolved by these classical methods.

T31058

17395-17475

Sentence

denotes

Also virus-triggered secondary PPIs are not resolved by these classical methods.

TextSentencer_T122

17476-17692

Sentence

denotes

The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.

TextSentencer_T122

17476-17692

Sentence

denotes

The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.

T94027

17476-17692

Sentence

denotes

The development of shotgun proteomics techniques described below thus presents a major breakthrough, which holds the promise of detecting higher order, reduced affinity and even transient virus receptor interactions.

TextSentencer_T123

17693-17821

Sentence

denotes

In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.

TextSentencer_T123

17693-17821

Sentence

denotes

In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.

T93080

17693-17821

Sentence

denotes

In the past decade, the development of quantitative shotgun proteomics techniques revolutionized the protein interactions field.

TextSentencer_T124

17822-18038

Sentence

denotes

In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.

TextSentencer_T124

17822-18038

Sentence

denotes

In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.

T24049

17822-18038

Sentence

denotes

In contrast to previous qualitative approaches, shotgun techniques avoid extensive purification from gels and instead analyze a complex mixture of proteins, thereby tremendously increasing sensitivity and throughput.

TextSentencer_T125

18039-18289

Sentence

denotes

Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.

TextSentencer_T125

18039-18289

Sentence

denotes

Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.

T84518

18039-18289

Sentence

denotes

Technological development of high performance liquid chromatography (LC) and ultra-high resolution ion trap MS together reduced measurement time, increased peptide sensitivity and measurement reproducibility and thus made shotgun techniques possible.

TextSentencer_T126

18290-18493

Sentence

denotes

Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).

TextSentencer_T126

18290-18493

Sentence

denotes

Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).

T80104

18290-18493

Sentence

denotes

Moreover, mass accuracy of new generation ion trap mass spectrometers increased up to 0.001 Da, guaranteeing high confidence peptide identification and analysis of posttranslational modifications (PTMs).

TextSentencer_T127

18494-18696

Sentence

denotes

LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .

TextSentencer_T127

18494-18696

Sentence

denotes

LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .

T85588

18494-18696

Sentence

denotes

LC-MS thus emerged as prime in depth proteomics method leaving behind alternative techniques like two-dimensional gel electrophoresis, low-resolution MALDI and protein arrays (Mann and Kelleher, 2008) .

TextSentencer_T128

18697-18833

Sentence

denotes

Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.

TextSentencer_T128

18697-18833

Sentence

denotes

Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.

T8609

18697-18833

Sentence

denotes

Shortly, in shotgun interaction proteomics affinity enriched protein mixtures are as a whole digested to peptides and analyzed by LC-MS.

TextSentencer_T129

18834-18999

Sentence

denotes

To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .

TextSentencer_T129

18834-18999

Sentence

denotes

To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .

T16077

18834-18999

Sentence

denotes

To separate the specific binding partners from the excess of background proteins, specific and control purifications are directly compared (Vermeulen et al., 2008) .

TextSentencer_T130

19000-19205

Sentence

denotes

This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.

TextSentencer_T130

19000-19205

Sentence

denotes

This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.

T9823

19000-19205

Sentence

denotes

This is achieved either by stable isotope labeling of amino acids in culture (SILAC) or by the more recent computational based label-free quantification methods (LFQ) described in the subsequent paragraph.

TextSentencer_T131

19206-19327

Sentence

denotes

Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).

TextSentencer_T131

19206-19327

Sentence

denotes

Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).

T46611

19206-19327

Sentence

denotes

Most recent techniques use one-step AE protocols, which preserve weak and transient interactions (see below for details).

TextSentencer_T132

19328-19458

Sentence

denotes

Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.

TextSentencer_T132

19328-19458

Sentence

denotes

Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.

T34880

19328-19458

Sentence

denotes

Fig. 1 highlights the milestones in the development of MS-based proteomics techniques and Box 2 describes common proteomics terms.

TextSentencer_T133

19459-19823

Sentence

denotes

While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .

TextSentencer_T133

19459-19823

Sentence

denotes

While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .

T22103

19459-19823

Sentence

denotes

While quantitative shotgun proteomics has been used in a variety of fields including signal transduction, cell adhesion and even viral immune modulation, we are just starting to appreciate its power for the study of the viral replication cycle and in particular virus entry (Kruger et al., 2008; Pichlmair et al., 2012; Weekes et al., 2014; Zanivan et al., 2013) .

TextSentencer_T134

19824-19945

Sentence

denotes

MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.

TextSentencer_T134

19824-19945

Sentence

denotes

MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.

T20259

19824-19945

Sentence

denotes

MS based methods are commonly used to identify and quantify proteins, to profile protein-interactions or whole proteomes.

TextSentencer_T135

19946-20177

Sentence

denotes

Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .

TextSentencer_T135

19946-20177

Sentence

denotes

Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .

T13519

19946-20177

Sentence

denotes

Therefore, proteins are isolated and proteolytically digested, the resulting peptides are separated via LC, and then analyzed by tandem mass spectrometry (MS/MS) (bottom-up approach or shotgun proteomics) (Vermeulen et al., 2008) .

TextSentencer_T136

20178-20315

Sentence

denotes

Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).

TextSentencer_T136

20178-20315

Sentence

denotes

Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).

T42464

20178-20315

Sentence

denotes

Alternatively a top-down approach can be used, where the protein is fragmented during the mass spectrometric analysis (Boeri Erba, 2014).

TextSentencer_T137

20316-20463

Sentence

denotes

For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:

TextSentencer_T137

20316-20463

Sentence

denotes

For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:

T22111

20316-20463

Sentence

denotes

For quantitative proteomics, most often bottom-up high resolution MS techniques are used in combination with either labeling or label-free methods:

TextSentencer_T138

20464-20585

Sentence

denotes

A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .

TextSentencer_T138

20464-20585

Sentence

denotes

A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .

T19987

20464-20585

Sentence

denotes

A powerful and the most commonly used label-based method for the quantification of proteins is SILAC (Ong et al., 2002) .

TextSentencer_T139

20586-20680

Sentence

denotes

In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.

TextSentencer_T139

20586-20680

Sentence

denotes

In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.

T56270

20586-20680

Sentence

denotes

In short, an isotope label is metabolically incorporated into peptides and proteins of a cell.

TextSentencer_T140

20681-20844

Sentence

denotes

Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.

TextSentencer_T140

20681-20844

Sentence

denotes

Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.

T58549

20681-20844

Sentence

denotes

Typically, essential amino acids with heavy isotopes (e.g., 15 N, 13 C) are fed to cells over several passages until nearly all unlabeled amino acids are replaced.

TextSentencer_T141

20845-21026

Sentence

denotes

As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.

TextSentencer_T141

20845-21026

Sentence

denotes

As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.

T22452

20845-21026

Sentence

denotes

As the physicochem- ical properties of light and heavy amino acids are nearly identical, cells labeled with the isotopic analogs behave similar or even identical to unlabeled cells.

TextSentencer_T142

21027-21276

Sentence

denotes

Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .

TextSentencer_T142

21027-21276

Sentence

denotes

Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .

T39728

21027-21276

Sentence

denotes

Based on the isotope label SILAC allows the direct comparison of two cell populations (heavy and light) from two distinct experimental conditions; for instance, from cells with surface-bound virus or cells without bound virus (Gerold et al., 2015) .

TextSentencer_T143

21277-21409

Sentence

denotes

Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.

TextSentencer_T143

21277-21409

Sentence

denotes

Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.

T20011

21277-21409

Sentence

denotes

Prior to proteomic analysis, i.e., whole cell lysate analysis or AP of protein complexes, the differently labeled samples are mixed.

TextSentencer_T144

21410-21501

Sentence

denotes

This is advantageous as all samples are processed equally excluding sample handling biases.

TextSentencer_T144

21410-21501

Sentence

denotes

This is advantageous as all samples are processed equally excluding sample handling biases.

T28781

21410-21501

Sentence

denotes

This is advantageous as all samples are processed equally excluding sample handling biases.

TextSentencer_T145

21502-21597

Sentence

denotes

Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.

TextSentencer_T145

21502-21597

Sentence

denotes

Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.

T54018

21502-21597

Sentence

denotes

Proteins are then digested, peptides reduced and alkylated, separated by LC and analyzed by MS.

TextSentencer_T146

21598-21709

Sentence

denotes

Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.

TextSentencer_T146

21598-21709

Sentence

denotes

Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.

T16361

21598-21709

Sentence

denotes

Peptides derived from heavy or light cells are subsequently differentiated by their characteristic mass offset.

TextSentencer_T147

21710-21841

Sentence

denotes

Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.

TextSentencer_T147

21710-21841

Sentence

denotes

Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.

T77066

21710-21841

Sentence

denotes

Relative abundances of proteins in each sample are calculated based on the heavy and light signal intensities in the same spectrum.

TextSentencer_T148

21842-21953

Sentence

denotes

Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.

TextSentencer_T148

21842-21953

Sentence

denotes

Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.

T63761

21842-21953

Sentence

denotes

Typically, SILAC is used for relative quantification of protein levels under two different cellular conditions.

TextSentencer_T149

21954-22110

Sentence

denotes

Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .

TextSentencer_T149

21954-22110

Sentence

denotes

Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .

T77827

21954-22110

Sentence

denotes

Of note, medium labeled amino acids are additionally available and allow expanding a SILAC experiment to three cellular conditions (Hilger and Mann, 2012) .

TextSentencer_T150

22111-22202

Sentence

denotes

The high accuracy of SILAC typically requires analysis of only two experimental replicates.

TextSentencer_T150

22111-22202

Sentence

denotes

The high accuracy of SILAC typically requires analysis of only two experimental replicates.

T72792

22111-22202

Sentence

denotes

The high accuracy of SILAC typically requires analysis of only two experimental replicates.

TextSentencer_T151

22203-22309

Sentence

denotes

In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.

TextSentencer_T151

22203-22309

Sentence

denotes

In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.

T24098

22203-22309

Sentence

denotes

In addition, two replicates of a label swap experimental condition allow assessing label-specific effects.

TextSentencer_T152

22310-22415

Sentence

denotes

Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.

TextSentencer_T152

22310-22415

Sentence

denotes

Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.

T55917

22310-22415

Sentence

denotes

Thus, a typical dual SILAC experiment starts with eight experimental samples mixed into four SILAC pairs.

TextSentencer_T153

22416-22582

Sentence

denotes

Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).

TextSentencer_T153

22416-22582

Sentence

denotes

Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).

T26826

22416-22582

Sentence

denotes

Those are duplicates of the forward label pair (light-condition 1; heavy-condition 2) and duplicates of the reverse label pair (light-condition 2; heavy-condition 1).

TextSentencer_T154

22583-22618

Sentence

denotes

Fig. 3A depicts the SILAC workflow.

TextSentencer_T154

22583-22618

Sentence

denotes

Fig. 3A depicts the SILAC workflow.

T45285

22583-22618

Sentence

denotes

Fig. 3A depicts the SILAC workflow.

TextSentencer_T155

22619-22687

Sentence

denotes

SILAC followed by LC-MS/MS can answer various questions in virology.

TextSentencer_T155

22619-22687

Sentence

denotes

SILAC followed by LC-MS/MS can answer various questions in virology.

T17055

22619-22687

Sentence

denotes

SILAC followed by LC-MS/MS can answer various questions in virology.

TextSentencer_T156

22688-22814

Sentence

denotes

For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .

TextSentencer_T156

22688-22814

Sentence

denotes

For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .

T1662

22688-22814

Sentence

denotes

For example, it can be used to compare the proteome of uninfected to that of virus infected cells (e.g., Zhang et al., 2013) .

TextSentencer_T157

22815-22966

Sentence

denotes

Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .

TextSentencer_T157

22815-22966

Sentence

denotes

Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .

T53415

22815-22966

Sentence

denotes

Also cells at different time points post infection can be analyzed to understand how viruses alter host cell protein expression (Weekes et al., 2014) .

TextSentencer_T158

22967-23190

Sentence

denotes

For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .

TextSentencer_T158

22967-23190

Sentence

denotes

For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .

T82133

22967-23190

Sentence

denotes

For instance, Berard et al. performed a temporal quantification of cells infected with herpes simplex virus type 1 (HSV1) and by this showed how HSV1 modulates the metabolic function of the host cell (Berard et al., 2015) .

TextSentencer_T159

23191-23587

Sentence

denotes

Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .

TextSentencer_T159

23191-23587

Sentence

denotes

Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .

T69945

23191-23587

Sentence

denotes

Beside this, SILAC followed by LC-MS/MS can also be used to identify cellular targets of viral enzymes, as it has been done for the identification of the HCV protease NS3-4A targets: by comparing whole proteomes from hepatoma cells with and without the NS3-4A protease, Morikawa et al. discovered that 'probable glutathione peroxidase 8' is cleaved by the viral protease (Morikawa et al., 2014) .

TextSentencer_T160

23588-23687

Sentence

denotes

SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.

TextSentencer_T160

23588-23687

Sentence

denotes

SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.

T21335

23588-23687

Sentence

denotes

SILAC is also suitable to analyze how viruses alter the proteome of distinct cellular compartments.

TextSentencer_T161

23688-23801

Sentence

denotes

For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .

TextSentencer_T161

23688-23801

Sentence

denotes

For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .

T20070

23688-23801

Sentence

denotes

For instance, Xie et al. defined the modification of lipid raft composition in HBV infection (Xie et al., 2012) .

TextSentencer_T162

23802-24029

Sentence

denotes

In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).

TextSentencer_T162

23802-24029

Sentence

denotes

In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).

T45508

23802-24029

Sentence

denotes

In combination with AP of a protein of interest, SILAC followed by LC-MS/MS can also discover protein-interactions and dynamic changes in interaction complexes (reviewed e.g., in (Gingras et al., 2007; Trinkle-Mulcahy, 2012) ).

TextSentencer_T163

24030-24172

Sentence

denotes

High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.

TextSentencer_T163

24030-24172

Sentence

denotes

High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.

T4723

24030-24172

Sentence

denotes

High-throughput AP-MS has led to important findings regarding virus entry, for instance the identification of receptors or receptor-complexes.

TextSentencer_T164

24173-24353

Sentence

denotes

A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .

TextSentencer_T164

24173-24353

Sentence

denotes

A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .

T97054

24173-24353

Sentence

denotes

A successful example is the AP-MS analysis of the HCV receptor CD81, which revealed HRas as a CD81-binding partner and signaling molecule needed for HCV entry (Zona et al., 2013) .

TextSentencer_T165

24354-24449

Sentence

denotes

A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.

TextSentencer_T165

24354-24449

Sentence

denotes

A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.

T58147

24354-24449

Sentence

denotes

A clear benefit of SILAC is its high reproducibility, robustness and relatively easy execution.

TextSentencer_T166

24450-24519

Sentence

denotes

SILAC is applicable to most cell culture cells and sample conditions.

TextSentencer_T166

24450-24519

Sentence

denotes

SILAC is applicable to most cell culture cells and sample conditions.

T11899

24450-24519

Sentence

denotes

SILAC is applicable to most cell culture cells and sample conditions.

TextSentencer_T167

24520-24624

Sentence

denotes

Even SILAC mice have been developed in the past for ex vivo proteomics analyses (Zanivan et al., 2012) .

TextSentencer_T167

24520-24624

Sentence

denotes

Even SILAC mice have been developed in the past for ex vivo proteomics analyses (Zanivan et al., 2012) .

T89806

24520-24624

Sentence

denotes

Even SILAC mice have been developed in the past for ex vivo proteomics analyses (Zanivan et al., 2012) .

TextSentencer_T168

24625-24631

Sentence

denotes

Box 2:

TextSentencer_T168

24625-24631

Sentence

denotes

Box 2:

T4718

24625-24631

Sentence

denotes

Box 2:

TextSentencer_T169

24632-24700

Sentence

denotes

Definitions and abbreviations in mass spectrometry based proteomics.

TextSentencer_T169

24632-24700

Sentence

denotes

Definitions and abbreviations in mass spectrometry based proteomics.

T57660

24632-24700

Sentence

denotes

Definitions and abbreviations in mass spectrometry based proteomics.

TextSentencer_T170

24701-24787

Sentence

denotes

Proteome: entity of proteins expressed at a given cellular state or in a given tissue.

TextSentencer_T170

24701-24787

Sentence

denotes

Proteome: entity of proteins expressed at a given cellular state or in a given tissue.

T50739

24701-24787

Sentence

denotes

Proteome: entity of proteins expressed at a given cellular state or in a given tissue.

TextSentencer_T171

24788-24839

Sentence

denotes

The term was coined in analogy to 'genome' in 1996.

TextSentencer_T171

24788-24839

Sentence

denotes

The term was coined in analogy to 'genome' in 1996.

T30577

24788-24839

Sentence

denotes

The term was coined in analogy to 'genome' in 1996.

TextSentencer_T172

24840-24862

Sentence

denotes

MS: mass spectrometry.

TextSentencer_T172

24840-24862

Sentence

denotes

MS: mass spectrometry.

T43209

24840-24862

Sentence

denotes

MS: mass spectrometry.

TextSentencer_T173

24863-24982

Sentence

denotes

ESI: electrospray ionization; ionization technique based on spraying of a sample solution into a strong electric field.

TextSentencer_T173

24863-24982

Sentence

denotes

ESI: electrospray ionization; ionization technique based on spraying of a sample solution into a strong electric field.

T95616

24863-24982

Sentence

denotes

ESI: electrospray ionization; ionization technique based on spraying of a sample solution into a strong electric field.

TextSentencer_T174

24983-25192

Sentence

denotes

MALDI: matrix-assisted laser desorption/ionization; ionization technique based on mixing of samples with a matrix, which absorbs ultraviolet light and converts it to heat energy leading to sample vaporization.

TextSentencer_T174

24983-25192

Sentence

denotes

MALDI: matrix-assisted laser desorption/ionization; ionization technique based on mixing of samples with a matrix, which absorbs ultraviolet light and converts it to heat energy leading to sample vaporization.

T35236

24983-25192

Sentence

denotes

MALDI: matrix-assisted laser desorption/ionization; ionization technique based on mixing of samples with a matrix, which absorbs ultraviolet light and converts it to heat energy leading to sample vaporization.

TextSentencer_T175

25193-25367

Sentence

denotes

Bottom up proteomics: identification of proteins based on MS peptide fingerprints after digestion of a protein into peptides using a sequence-specific enzyme such as trypsin.

TextSentencer_T175

25193-25367

Sentence

denotes

Bottom up proteomics: identification of proteins based on MS peptide fingerprints after digestion of a protein into peptides using a sequence-specific enzyme such as trypsin.

T55966

25193-25367

Sentence

denotes

Bottom up proteomics: identification of proteins based on MS peptide fingerprints after digestion of a protein into peptides using a sequence-specific enzyme such as trypsin.

TextSentencer_T176

25368-25420

Sentence

denotes

Top down proteomics: MS analysis of entire proteins.

TextSentencer_T176

25368-25420

Sentence

denotes

Top down proteomics: MS analysis of entire proteins.

T39758

25368-25420

Sentence

denotes

Top down proteomics: MS analysis of entire proteins.

TextSentencer_T177

25421-25514

Sentence

denotes

Shotgun proteomics: bottom-up proteomics technique to identify proteins in a complex mixture.

TextSentencer_T177

25421-25514

Sentence

denotes

Shotgun proteomics: bottom-up proteomics technique to identify proteins in a complex mixture.

T56497

25421-25514

Sentence

denotes

Shotgun proteomics: bottom-up proteomics technique to identify proteins in a complex mixture.

TextSentencer_T178

25515-25627

Sentence

denotes

Proteins are digested to peptides, peptides separated by liquid chromatography and then identified by tandem MS.

TextSentencer_T178

25515-25627

Sentence

denotes

Proteins are digested to peptides, peptides separated by liquid chromatography and then identified by tandem MS.

T96317

25515-25627

Sentence

denotes

Proteins are digested to peptides, peptides separated by liquid chromatography and then identified by tandem MS.

TextSentencer_T179

25628-25761

Sentence

denotes

Quantitative proteomics: shotgun proteomics with the additional dimension of measuring the quantity of a protein in a complex sample.

TextSentencer_T179

25628-25761

Sentence

denotes

Quantitative proteomics: shotgun proteomics with the additional dimension of measuring the quantity of a protein in a complex sample.

T46818

25628-25761

Sentence

denotes

Quantitative proteomics: shotgun proteomics with the additional dimension of measuring the quantity of a protein in a complex sample.

TextSentencer_T180

25762-25855

Sentence

denotes

Relative quantities in two or more samples are determined either by SILAC or LFQ (see below).

TextSentencer_T180

25762-25855

Sentence

denotes

Relative quantities in two or more samples are determined either by SILAC or LFQ (see below).

T1400

25762-25855

Sentence

denotes

Relative quantities in two or more samples are determined either by SILAC or LFQ (see below).

TextSentencer_T181

25856-25992

Sentence

denotes

Absolute quantification can be achieved using spike in standards or a proteomics ruler (see paragraph on protein complex stoichiometry).

TextSentencer_T181

25856-25992

Sentence

denotes

Absolute quantification can be achieved using spike in standards or a proteomics ruler (see paragraph on protein complex stoichiometry).

T91629

25856-25992

Sentence

denotes

Absolute quantification can be achieved using spike in standards or a proteomics ruler (see paragraph on protein complex stoichiometry).

TextSentencer_T182

25993-26111

Sentence

denotes

Interaction proteomics: unbiased identification of protein-protein interactions by affinity enrichment followed by MS.

TextSentencer_T182

25993-26111

Sentence

denotes

Interaction proteomics: unbiased identification of protein-protein interactions by affinity enrichment followed by MS.

T45561

25993-26111

Sentence

denotes

Interaction proteomics: unbiased identification of protein-protein interactions by affinity enrichment followed by MS.

TextSentencer_T183

26112-26290

Sentence

denotes

SILAC: stable isotope labeling by amino acids in cell culture; first quantitative method for the comparison of cellular protein amounts in two to three different cellular states.

TextSentencer_T183

26112-26290

Sentence

denotes

SILAC: stable isotope labeling by amino acids in cell culture; first quantitative method for the comparison of cellular protein amounts in two to three different cellular states.

T92335

26112-26290

Sentence

denotes

SILAC: stable isotope labeling by amino acids in cell culture; first quantitative method for the comparison of cellular protein amounts in two to three different cellular states.

TextSentencer_T184

26291-26448

Sentence

denotes

SILAC is based on the isotope labeling of cellular proteins by feeding cells with heavy isotope amino acids (e.g. N-15 and C-13 labeled arginine and lysine).

TextSentencer_T184

26291-26448

Sentence

denotes

SILAC is based on the isotope labeling of cellular proteins by feeding cells with heavy isotope amino acids (e.g. N-15 and C-13 labeled arginine and lysine).

T85399

26291-26448

Sentence

denotes

SILAC is based on the isotope labeling of cellular proteins by feeding cells with heavy isotope amino acids (e.g. N-15 and C-13 labeled arginine and lysine).

TextSentencer_T185

26449-26676

Sentence

denotes

Label-free quantification (LFQ): quantitative proteomics technique based on either signal intensity measurement or spectral counting followed by computational matching of peptides from multiple samples and signal normalization.

TextSentencer_T185

26449-26676

Sentence

denotes

Label-free quantification (LFQ): quantitative proteomics technique based on either signal intensity measurement or spectral counting followed by computational matching of peptides from multiple samples and signal normalization.

T53278

26449-26676

Sentence

denotes

Label-free quantification (LFQ): quantitative proteomics technique based on either signal intensity measurement or spectral counting followed by computational matching of peptides from multiple samples and signal normalization.

TextSentencer_T186

26677-26711

Sentence

denotes

PPI: protein-protein interactions.

TextSentencer_T186

26677-26711

Sentence

denotes

PPI: protein-protein interactions.

T28055

26677-26711

Sentence

denotes

PPI: protein-protein interactions.

TextSentencer_T187

26712-26748

Sentence

denotes

PTM: posttranslational modification.

TextSentencer_T187

26712-26748

Sentence

denotes

PTM: posttranslational modification.

T65566

26712-26748

Sentence

denotes

PTM: posttranslational modification.

TextSentencer_T188

26749-26902

Sentence

denotes

Common protein modifications include among others phosphorylation, lipidation, glycosylation, methylation, acetylation, ubiquitinylation and SUMOylation.

TextSentencer_T188

26749-26902

Sentence

denotes

Common protein modifications include among others phosphorylation, lipidation, glycosylation, methylation, acetylation, ubiquitinylation and SUMOylation.

T32260

26749-26902

Sentence

denotes

Common protein modifications include among others phosphorylation, lipidation, glycosylation, methylation, acetylation, ubiquitinylation and SUMOylation.

TextSentencer_T189

26903-27091

Sentence

denotes

AP-MS: affinity purification of proteins using antibodies against endogenous epitopes or epitope tags followed by mass spectrometric identification or quantification of the bound proteins.

TextSentencer_T189

26903-27091

Sentence

denotes

AP-MS: affinity purification of proteins using antibodies against endogenous epitopes or epitope tags followed by mass spectrometric identification or quantification of the bound proteins.

T88171

26903-27091

Sentence

denotes

AP-MS: affinity purification of proteins using antibodies against endogenous epitopes or epitope tags followed by mass spectrometric identification or quantification of the bound proteins.

TextSentencer_T190

27092-27301

Sentence

denotes

AE-MS: affinity enrichment of proteins using fast single step methods, which preserve transient and low affinity interactions, followed by mass spectrometric identification or quantification of bound proteins.

TextSentencer_T190

27092-27301

Sentence

denotes

AE-MS: affinity enrichment of proteins using fast single step methods, which preserve transient and low affinity interactions, followed by mass spectrometric identification or quantification of bound proteins.

T72313

27092-27301

Sentence

denotes

AE-MS: affinity enrichment of proteins using fast single step methods, which preserve transient and low affinity interactions, followed by mass spectrometric identification or quantification of bound proteins.

TextSentencer_T191

27302-27469

Sentence

denotes

Caveats of SILAC are the limited sample number of maximum three and the additional labeling step requiring culturing of cells for two to three weeks prior to analysis.

TextSentencer_T191

27302-27469

Sentence

denotes

Caveats of SILAC are the limited sample number of maximum three and the additional labeling step requiring culturing of cells for two to three weeks prior to analysis.

T6173

27302-27469

Sentence

denotes

Caveats of SILAC are the limited sample number of maximum three and the additional labeling step requiring culturing of cells for two to three weeks prior to analysis.

TextSentencer_T192

27470-27565

Sentence

denotes

Thus some primary human cells, which rapidly dedifferentiate ex vivo, are not suited for SILAC.

TextSentencer_T192

27470-27565

Sentence

denotes

Thus some primary human cells, which rapidly dedifferentiate ex vivo, are not suited for SILAC.

T24380

27470-27565

Sentence

denotes

Thus some primary human cells, which rapidly dedifferentiate ex vivo, are not suited for SILAC.

TextSentencer_T193

27566-27656

Sentence

denotes

Similarly, clinical samples cannot be labeled and are thus not amenable to SILAC analysis.

TextSentencer_T193

27566-27656

Sentence

denotes

Similarly, clinical samples cannot be labeled and are thus not amenable to SILAC analysis.

T8224

27566-27656

Sentence

denotes

Similarly, clinical samples cannot be labeled and are thus not amenable to SILAC analysis.

TextSentencer_T194

27657-27716

Sentence

denotes

Increasingly popular alternatives to SILAC are LFQ methods.

TextSentencer_T194

27657-27716

Sentence

denotes

Increasingly popular alternatives to SILAC are LFQ methods.

T13877

27657-27716

Sentence

denotes

Increasingly popular alternatives to SILAC are LFQ methods.

TextSentencer_T195

27717-27804

Sentence

denotes

These can determine the relative or absolute abundance of a protein in complex samples.

TextSentencer_T195

27717-27804

Sentence

denotes

These can determine the relative or absolute abundance of a protein in complex samples.

T95671

27717-27804

Sentence

denotes

These can determine the relative or absolute abundance of a protein in complex samples.

TextSentencer_T196

27805-27993

Sentence

denotes

The first semi-quantitative labelfree method developed, which has since then been continuously refined, is based on the measurement of MS/MS peptide intensities (Bondarenko et al., 2002) .

TextSentencer_T196

27805-27993

Sentence

denotes

The first semi-quantitative labelfree method developed, which has since then been continuously refined, is based on the measurement of MS/MS peptide intensities (Bondarenko et al., 2002) .

T92112

27805-27993

Sentence

denotes

The first semi-quantitative labelfree method developed, which has since then been continuously refined, is based on the measurement of MS/MS peptide intensities (Bondarenko et al., 2002) .

TextSentencer_T197

27994-28196

Sentence

denotes

To this end, peak areas of all identified peptides from one protein are summed up and normalized to one or several proteins with constant concentration or even to all iden-tified proteins in the sample.

TextSentencer_T197

27994-28196

Sentence

denotes

To this end, peak areas of all identified peptides from one protein are summed up and normalized to one or several proteins with constant concentration or even to all iden-tified proteins in the sample.

T67104

27994-28196

Sentence

denotes

To this end, peak areas of all identified peptides from one protein are summed up and normalized to one or several proteins with constant concentration or even to all iden-tified proteins in the sample.

TextSentencer_T198

28197-28325

Sentence

denotes

Bondarenko et al. showed that there is a linear correlation of the abundance of a protein and its total reconstructed peak area.

TextSentencer_T198

28197-28325

Sentence

denotes

Bondarenko et al. showed that there is a linear correlation of the abundance of a protein and its total reconstructed peak area.

T78134

28197-28325

Sentence

denotes

Bondarenko et al. showed that there is a linear correlation of the abundance of a protein and its total reconstructed peak area.

TextSentencer_T199

28326-28412

Sentence

denotes

An alternative semi-quantitative method used is spectral sampling (Liu et al., 2004) .

TextSentencer_T199

28326-28412

Sentence

denotes

An alternative semi-quantitative method used is spectral sampling (Liu et al., 2004) .

T7558

28326-28412

Sentence

denotes

An alternative semi-quantitative method used is spectral sampling (Liu et al., 2004) .

TextSentencer_T200

28413-28594

Sentence

denotes

It was shown that highly abundant proteins are sampled more frequently by LC-MS/MS and that the spectral copy number obtained increases linearly with the concentration of a protein.

TextSentencer_T200

28413-28594

Sentence

denotes

It was shown that highly abundant proteins are sampled more frequently by LC-MS/MS and that the spectral copy number obtained increases linearly with the concentration of a protein.

T31875

28413-28594

Sentence

denotes

It was shown that highly abundant proteins are sampled more frequently by LC-MS/MS and that the spectral copy number obtained increases linearly with the concentration of a protein.

TextSentencer_T201

28595-28761

Sentence

denotes

Accordingly, the number of MS/MS spectra gained for one protein can be counted and compared between different samples measured using the same experimental conditions.

TextSentencer_T201

28595-28761

Sentence

denotes

Accordingly, the number of MS/MS spectra gained for one protein can be counted and compared between different samples measured using the same experimental conditions.

T93038

28595-28761

Sentence

denotes

Accordingly, the number of MS/MS spectra gained for one protein can be counted and compared between different samples measured using the same experimental conditions.

TextSentencer_T202

28762-29029

Sentence

denotes

Several computational approaches to predict specific protein interactions in label-free datasets have been developed, among them Significance Analysis of INTeractome (SAINT) and Mass spectrometry interaction STatistics (MiST) (Choi et al., 2011; Jager et al., 2012) .

TextSentencer_T202

28762-29029

Sentence

denotes

Several computational approaches to predict specific protein interactions in label-free datasets have been developed, among them Significance Analysis of INTeractome (SAINT) and Mass spectrometry interaction STatistics (MiST) (Choi et al., 2011; Jager et al., 2012) .

T92923

28762-29029

Sentence

denotes

Several computational approaches to predict specific protein interactions in label-free datasets have been developed, among them Significance Analysis of INTeractome (SAINT) and Mass spectrometry interaction STatistics (MiST) (Choi et al., 2011; Jager et al., 2012) .

TextSentencer_T203

29030-29246

Sentence

denotes

These tools compute interaction probabilities based on spectral counts of all interactions that a prey-bait pair is involved in or based on abundance, reproducibility and specificity of a preybait pair, respectively.

TextSentencer_T203

29030-29246

Sentence

denotes

These tools compute interaction probabilities based on spectral counts of all interactions that a prey-bait pair is involved in or based on abundance, reproducibility and specificity of a preybait pair, respectively.

T74513

29030-29246

Sentence

denotes

These tools compute interaction probabilities based on spectral counts of all interactions that a prey-bait pair is involved in or based on abundance, reproducibility and specificity of a preybait pair, respectively.

TextSentencer_T204

29247-29451

Sentence

denotes

Recent developments in MS technology and analysis algorithms now allow highly sensitive, efficient and robust intensity-based label-free protein quantification (reviewed e.g., in (Nahnsen et al., 2013) ).

TextSentencer_T204

29247-29451

Sentence

denotes

Recent developments in MS technology and analysis algorithms now allow highly sensitive, efficient and robust intensity-based label-free protein quantification (reviewed e.g., in (Nahnsen et al., 2013) ).

T63535

29247-29451

Sentence

denotes

Recent developments in MS technology and analysis algorithms now allow highly sensitive, efficient and robust intensity-based label-free protein quantification (reviewed e.g., in (Nahnsen et al., 2013) ).

TextSentencer_T205

29452-29523

Sentence

denotes

For this, samples are processed in parallel and not mixed, as in SILAC.

TextSentencer_T205

29452-29523

Sentence

denotes

For this, samples are processed in parallel and not mixed, as in SILAC.

T87863

29452-29523

Sentence

denotes

For this, samples are processed in parallel and not mixed, as in SILAC.

TextSentencer_T206

29524-29577

Sentence

denotes

Thus, an unlimited number of samples can be compared.

TextSentencer_T206

29524-29577

Sentence

denotes

Thus, an unlimited number of samples can be compared.

T97549

29524-29577

Sentence

denotes

Thus, an unlimited number of samples can be compared.

TextSentencer_T207

29578-29768

Sentence

denotes

Normalization is achieved post LC-MS/MS analysis by comparing all peptide signals from all MS runs and assuming that most protein signals remain unaltered in the different sample conditions.

TextSentencer_T207

29578-29768

Sentence

denotes

Normalization is achieved post LC-MS/MS analysis by comparing all peptide signals from all MS runs and assuming that most protein signals remain unaltered in the different sample conditions.

T65181

29578-29768

Sentence

denotes

Normalization is achieved post LC-MS/MS analysis by comparing all peptide signals from all MS runs and assuming that most protein signals remain unaltered in the different sample conditions.

TextSentencer_T208

29769-29809

Sentence

denotes

Thus, no external standards are needed .

TextSentencer_T208

29769-29809

Sentence

denotes

Thus, no external standards are needed .

T38218

29769-29809

Sentence

denotes

Thus, no external standards are needed .

TextSentencer_T209

29810-29942

Sentence

denotes

However, acquisition of accurate datasets requires the analysis of at least three, typically four, biological replicates (Fig. 3B ).

TextSentencer_T209

29810-29942

Sentence

denotes

However, acquisition of accurate datasets requires the analysis of at least three, typically four, biological replicates (Fig. 3B ).

T851

29810-29942

Sentence

denotes

However, acquisition of accurate datasets requires the analysis of at least three, typically four, biological replicates (Fig. 3B ).

TextSentencer_T210

29943-30173

Sentence

denotes

MS combined with LFQ algorithms is suitable for virological research and has been used e.g., to show that subsets of dendritic cells (DCs) differ in their ability to sense single stranded RNA (ssRNA) viruses (Luber et al., 2010) .

TextSentencer_T210

29943-30173

Sentence

denotes

MS combined with LFQ algorithms is suitable for virological research and has been used e.g., to show that subsets of dendritic cells (DCs) differ in their ability to sense single stranded RNA (ssRNA) viruses (Luber et al., 2010) .

T28151

29943-30173

Sentence

denotes

MS combined with LFQ algorithms is suitable for virological research and has been used e.g., to show that subsets of dendritic cells (DCs) differ in their ability to sense single stranded RNA (ssRNA) viruses (Luber et al., 2010) .

TextSentencer_T211

30174-30283

Sentence

denotes

Briefly, Luber at al. compared the whole cell proteome of DC subsets by high-resolution MS combined with LFQ.

TextSentencer_T211

30174-30283

Sentence

denotes

Briefly, Luber at al. compared the whole cell proteome of DC subsets by high-resolution MS combined with LFQ.

T99266

30174-30283

Sentence

denotes

Briefly, Luber at al. compared the whole cell proteome of DC subsets by high-resolution MS combined with LFQ.

TextSentencer_T212

30284-30493

Sentence

denotes

They found, that DC subsets differently express proteins involved in pattern recognition pathways and that this correlates with their ability to sense ssRNA viruses, such as Sendai virus and influenza A virus.

TextSentencer_T212

30284-30493

Sentence

denotes

They found, that DC subsets differently express proteins involved in pattern recognition pathways and that this correlates with their ability to sense ssRNA viruses, such as Sendai virus and influenza A virus.

T3537

30284-30493

Sentence

denotes

They found, that DC subsets differently express proteins involved in pattern recognition pathways and that this correlates with their ability to sense ssRNA viruses, such as Sendai virus and influenza A virus.

TextSentencer_T213

30494-30558

Sentence

denotes

Label-free methods also allow the analysis of protein complexes.

TextSentencer_T213

30494-30558

Sentence

denotes

Label-free methods also allow the analysis of protein complexes.

T17296

30494-30558

Sentence

denotes

Label-free methods also allow the analysis of protein complexes.

TextSentencer_T214

30559-30657

Sentence

denotes

Importantly, extensive purification of complexes prior to LC-MS/MS is no longer necessary for LFQ.

TextSentencer_T214

30559-30657

Sentence

denotes

Importantly, extensive purification of complexes prior to LC-MS/MS is no longer necessary for LFQ.

T32651

30559-30657

Sentence

denotes

Importantly, extensive purification of complexes prior to LC-MS/MS is no longer necessary for LFQ.

TextSentencer_T215

30658-30765

Sentence

denotes

Instead one AE step is sufficient for precise complex profiling, when controls are designed appropriately .

TextSentencer_T215

30658-30765

Sentence

denotes

Instead one AE step is sufficient for precise complex profiling, when controls are designed appropriately .

T91950

30658-30765

Sentence

denotes

Instead one AE step is sufficient for precise complex profiling, when controls are designed appropriately .

TextSentencer_T216

30766-30977

Sentence

denotes

False positive interaction partners, which are proteins unspecifically binding to the affinity resin, are computationally eliminated by comparing datasets to those of a control AE sample from cells without bait.

TextSentencer_T216

30766-30977

Sentence

denotes

False positive interaction partners, which are proteins unspecifically binding to the affinity resin, are computationally eliminated by comparing datasets to those of a control AE sample from cells without bait.

T26732

30766-30977

Sentence

denotes

False positive interaction partners, which are proteins unspecifically binding to the affinity resin, are computationally eliminated by comparing datasets to those of a control AE sample from cells without bait.

TextSentencer_T217

30978-31027

Sentence

denotes

Fig. 3B outlines the here described LFQ workflow.

TextSentencer_T217

30978-31027

Sentence

denotes

Fig. 3B outlines the here described LFQ workflow.

T48760

30978-31027

Sentence

denotes

Fig. 3B outlines the here described LFQ workflow.

TextSentencer_T218

31028-31374

Sentence

denotes

When compared to label-based methods, LFQ techniques have several advantages: nearly all kinds of samples can be measured, including clinical material and primary cells; sample number is unlimited; no special sample processing steps are needed; slight differences in sample preparation and measurement between the different samples are tolerated.

TextSentencer_T218

31028-31374

Sentence

denotes

When compared to label-based methods, LFQ techniques have several advantages: nearly all kinds of samples can be measured, including clinical material and primary cells; sample number is unlimited; no special sample processing steps are needed; slight differences in sample preparation and measurement between the different samples are tolerated.

T91122

31028-31374

Sentence

denotes

When compared to label-based methods, LFQ techniques have several advantages: nearly all kinds of samples can be measured, including clinical material and primary cells; sample number is unlimited; no special sample processing steps are needed; slight differences in sample preparation and measurement between the different samples are tolerated.

TextSentencer_T219

31375-31516

Sentence

denotes

Both, labeling and label-free quantification methods identify and quantify proteins with high confidence and lead to highly accurate results.

TextSentencer_T219

31375-31516

Sentence

denotes

Both, labeling and label-free quantification methods identify and quantify proteins with high confidence and lead to highly accurate results.

T31054

31375-31516

Sentence

denotes

Both, labeling and label-free quantification methods identify and quantify proteins with high confidence and lead to highly accurate results.

TextSentencer_T220

31517-31733

Sentence

denotes

Each step of the proteomics workflow can be quality controlled, e.g., by immunoblotting, computational analysis of peptide intensity distributions, and clustering analysis of biological replicate datasets (Fig. 3C ).

TextSentencer_T220

31517-31733

Sentence

denotes

Each step of the proteomics workflow can be quality controlled, e.g., by immunoblotting, computational analysis of peptide intensity distributions, and clustering analysis of biological replicate datasets (Fig. 3C ).

T42161

31517-31733

Sentence

denotes

Each step of the proteomics workflow can be quality controlled, e.g., by immunoblotting, computational analysis of peptide intensity distributions, and clustering analysis of biological replicate datasets (Fig. 3C ).

TextSentencer_T221

31734-31793

Sentence

denotes

To study virus entry both SILAC and LFQ are valuable tools.

TextSentencer_T221

31734-31793

Sentence

denotes

To study virus entry both SILAC and LFQ are valuable tools.

T13798

31734-31793

Sentence

denotes

To study virus entry both SILAC and LFQ are valuable tools.

TextSentencer_T222

31794-31866

Sentence

denotes

LFQ is ideally suited to study steady state virus receptor interactions.

TextSentencer_T222

31794-31866

Sentence

denotes

LFQ is ideally suited to study steady state virus receptor interactions.

T63477

31794-31866

Sentence

denotes

LFQ is ideally suited to study steady state virus receptor interactions.

TextSentencer_T223

31867-31984

Sentence

denotes

To this end, virus receptor-complexes are purified from cells expressing the receptor and cells lacking the receptor.

TextSentencer_T223

31867-31984

Sentence

denotes

To this end, virus receptor-complexes are purified from cells expressing the receptor and cells lacking the receptor.

T42949

31867-31984

Sentence

denotes

To this end, virus receptor-complexes are purified from cells expressing the receptor and cells lacking the receptor.

TextSentencer_T224

31985-32086

Sentence

denotes

Comparison of both datasets then allows to define receptor interacting proteins in a given cell line.

TextSentencer_T224

31985-32086

Sentence

denotes

Comparison of both datasets then allows to define receptor interacting proteins in a given cell line.

T16764

31985-32086

Sentence

denotes

Comparison of both datasets then allows to define receptor interacting proteins in a given cell line.

TextSentencer_T225

32087-32242

Sentence

denotes

SILAC on the other hand can sensitively distinguish low degree quantitative changes, as they occur when virus receptor complexes change upon virus binding.

TextSentencer_T225

32087-32242

Sentence

denotes

SILAC on the other hand can sensitively distinguish low degree quantitative changes, as they occur when virus receptor complexes change upon virus binding.

T16593

32087-32242

Sentence

denotes

SILAC on the other hand can sensitively distinguish low degree quantitative changes, as they occur when virus receptor complexes change upon virus binding.

TextSentencer_T226

32243-32380

Sentence

denotes

Briefly, heavy labeled cells are incubated with virus and light cells are left untreated (forward label); and vice versa (reverse label).

TextSentencer_T226

32243-32380

Sentence

denotes

Briefly, heavy labeled cells are incubated with virus and light cells are left untreated (forward label); and vice versa (reverse label).

T26208

32243-32380

Sentence

denotes

Briefly, heavy labeled cells are incubated with virus and light cells are left untreated (forward label); and vice versa (reverse label).

TextSentencer_T227

32381-32537

Sentence

denotes

After sample mixing, AP of receptor complexes and LC-MS analysis, changes in interaction strength of each protein in the receptor complex can be determined.

TextSentencer_T227

32381-32537

Sentence

denotes

After sample mixing, AP of receptor complexes and LC-MS analysis, changes in interaction strength of each protein in the receptor complex can be determined.

T46033

32381-32537

Sentence

denotes

After sample mixing, AP of receptor complexes and LC-MS analysis, changes in interaction strength of each protein in the receptor complex can be determined.

TextSentencer_T228

32538-32829

Sentence

denotes

Importantly, the untreated control should ideally contain all extracellular components as the virus sample, i.e. the ideal control is incubation with virus, which had been neutralized by blocking antibodies, or incubation with a "mock" virus preparation if such antibodies are not available.

TextSentencer_T228

32538-32829

Sentence

denotes

Importantly, the untreated control should ideally contain all extracellular components as the virus sample, i.e. the ideal control is incubation with virus, which had been neutralized by blocking antibodies, or incubation with a "mock" virus preparation if such antibodies are not available.

T52385

32538-32829

Sentence

denotes

Importantly, the untreated control should ideally contain all extracellular components as the virus sample, i.e. the ideal control is incubation with virus, which had been neutralized by blocking antibodies, or incubation with a "mock" virus preparation if such antibodies are not available.

TextSentencer_T229

32830-32931

Sentence

denotes

Using SILAC, we recently identified transient, virus-triggered interactions of the HCV receptor CD81.

TextSentencer_T229

32830-32931

Sentence

denotes

Using SILAC, we recently identified transient, virus-triggered interactions of the HCV receptor CD81.

T68389

32830-32931

Sentence

denotes

Using SILAC, we recently identified transient, virus-triggered interactions of the HCV receptor CD81.

TextSentencer_T230

32932-33081

Sentence

denotes

Among the 26 dynamic CD81 interactors we identified serum response factor binding protein 1 as a host factor aiding HCV entry (Gerold et al., 2015) .

TextSentencer_T230

32932-33081

Sentence

denotes

Among the 26 dynamic CD81 interactors we identified serum response factor binding protein 1 as a host factor aiding HCV entry (Gerold et al., 2015) .

T40812

32932-33081

Sentence

denotes

Among the 26 dynamic CD81 interactors we identified serum response factor binding protein 1 as a host factor aiding HCV entry (Gerold et al., 2015) .

TextSentencer_T231

33082-33155

Sentence

denotes

Of note, similar studies will soon be possible with advanced LFQ methods.

TextSentencer_T231

33082-33155

Sentence

denotes

Of note, similar studies will soon be possible with advanced LFQ methods.

T23992

33082-33155

Sentence

denotes

Of note, similar studies will soon be possible with advanced LFQ methods.

TextSentencer_T232

33156-33279

Sentence

denotes

Fig. 3 illustrates how quantitative proteomics can identify steady state and dynamic virus-triggered receptor interactions.

TextSentencer_T232

33156-33279

Sentence

denotes

Fig. 3 illustrates how quantitative proteomics can identify steady state and dynamic virus-triggered receptor interactions.

T69987

33156-33279

Sentence

denotes

Fig. 3 illustrates how quantitative proteomics can identify steady state and dynamic virus-triggered receptor interactions.

TextSentencer_T233

33280-33413

Sentence

denotes

In summary, SILAC and LFQ are powerful tools for analyzing virus-host interactions and global proteomic changes upon virus infection.

TextSentencer_T233

33280-33413

Sentence

denotes

In summary, SILAC and LFQ are powerful tools for analyzing virus-host interactions and global proteomic changes upon virus infection.

T66120

33280-33413

Sentence

denotes

In summary, SILAC and LFQ are powerful tools for analyzing virus-host interactions and global proteomic changes upon virus infection.

TextSentencer_T234

33414-33670

Sentence

denotes

Due to the recent improvements in high resolution MS and label-free analysis tools, the highly accurate, cost effective and broadly applicable LFQ methods will soon become the method of choice for profiling proteins, their interactions and whole proteomes.

TextSentencer_T234

33414-33670

Sentence

denotes

Due to the recent improvements in high resolution MS and label-free analysis tools, the highly accurate, cost effective and broadly applicable LFQ methods will soon become the method of choice for profiling proteins, their interactions and whole proteomes.

T19359

33414-33670

Sentence

denotes

Due to the recent improvements in high resolution MS and label-free analysis tools, the highly accurate, cost effective and broadly applicable LFQ methods will soon become the method of choice for profiling proteins, their interactions and whole proteomes.

TextSentencer_T235

33671-33794

Sentence

denotes

Steady state interactions of cellular proteins, which preexist before virus attachment, can be crucial for virus infection.

TextSentencer_T235

33671-33794

Sentence

denotes

Steady state interactions of cellular proteins, which preexist before virus attachment, can be crucial for virus infection.

T80468

33671-33794

Sentence

denotes

Steady state interactions of cellular proteins, which preexist before virus attachment, can be crucial for virus infection.

TextSentencer_T236

33795-33856

Sentence

denotes

This has been shown in the past mainly by biochemical assays.

TextSentencer_T236

33795-33856

Sentence

denotes

This has been shown in the past mainly by biochemical assays.

T2200

33795-33856

Sentence

denotes

This has been shown in the past mainly by biochemical assays.

TextSentencer_T237

33857-34039

Sentence

denotes

For instance, the interaction of moesin and CD46, which is needed for measles virus entry, was demonstrated by AP followed by immunoblot analysis (Schneider-Schaulies et al., 1995) .

TextSentencer_T237

33857-34039

Sentence

denotes

For instance, the interaction of moesin and CD46, which is needed for measles virus entry, was demonstrated by AP followed by immunoblot analysis (Schneider-Schaulies et al., 1995) .

T28860

33857-34039

Sentence

denotes

For instance, the interaction of moesin and CD46, which is needed for measles virus entry, was demonstrated by AP followed by immunoblot analysis (Schneider-Schaulies et al., 1995) .

TextSentencer_T238

34040-34240

Sentence

denotes

Since MSbased proteomics became the method of choice to analyze protein interactions, several studies used mostly non-quantitative proteomic techniques to characterize interactions of virus receptors.

TextSentencer_T238

34040-34240

Sentence

denotes

Since MSbased proteomics became the method of choice to analyze protein interactions, several studies used mostly non-quantitative proteomic techniques to characterize interactions of virus receptors.

T79092

34040-34240

Sentence

denotes

Since MSbased proteomics became the method of choice to analyze protein interactions, several studies used mostly non-quantitative proteomic techniques to characterize interactions of virus receptors.

TextSentencer_T239

34241-34448

Sentence

denotes

For example Chakraborty et al. (2012) analyzed immuoprecipitates of the Kaposiís sarcoma-associated herpesvirus (KSHV) receptor and lipid raft protein integrin ␣3␤1 via SDS-PAGE and MS of selected gel bands.

TextSentencer_T239

34241-34448

Sentence

denotes

For example Chakraborty et al. (2012) analyzed immuoprecipitates of the Kaposiís sarcoma-associated herpesvirus (KSHV) receptor and lipid raft protein integrin ␣3␤1 via SDS-PAGE and MS of selected gel bands.

T92245

34241-34448

Sentence

denotes

For example Chakraborty et al. (2012) analyzed immuoprecipitates of the Kaposiís sarcoma-associated herpesvirus (KSHV) receptor and lipid raft protein integrin ␣3␤1 via SDS-PAGE and MS of selected gel bands.

TextSentencer_T240

34449-34537

Sentence

denotes

They identified the association of integrin ␣3␤1 with several proteins, including EphA2.

TextSentencer_T240

34449-34537

Sentence

denotes

They identified the association of integrin ␣3␤1 with several proteins, including EphA2.

T59495

34449-34537

Sentence

denotes

They identified the association of integrin ␣3␤1 with several proteins, including EphA2.

TextSentencer_T241

34538-34687

Sentence

denotes

The identified associations were enriched in lipid rafts of KSHV infected human dermal microvascular endothelial cells, compared to uninfected cells.

TextSentencer_T241

34538-34687

Sentence

denotes

The identified associations were enriched in lipid rafts of KSHV infected human dermal microvascular endothelial cells, compared to uninfected cells.

T68772

34538-34687

Sentence

denotes

The identified associations were enriched in lipid rafts of KSHV infected human dermal microvascular endothelial cells, compared to uninfected cells.

TextSentencer_T242

34688-34868

Sentence

denotes

With virological assays Chakraborty et al. then showed that this enrichment is important for effective KSHV infection, especially for macropinocytosis and trafficking of the virus.

TextSentencer_T242

34688-34868

Sentence

denotes

With virological assays Chakraborty et al. then showed that this enrichment is important for effective KSHV infection, especially for macropinocytosis and trafficking of the virus.

T29011

34688-34868

Sentence

denotes

With virological assays Chakraborty et al. then showed that this enrichment is important for effective KSHV infection, especially for macropinocytosis and trafficking of the virus.

TextSentencer_T243

34869-35071

Sentence

denotes

Also quantitative MS-based techniques in combination with traditional virological assays can be used to decipher the role of steady state protein interactions in different steps of the viral life cycle.

TextSentencer_T243

34869-35071

Sentence

denotes

Also quantitative MS-based techniques in combination with traditional virological assays can be used to decipher the role of steady state protein interactions in different steps of the viral life cycle.

T88286

34869-35071

Sentence

denotes

Also quantitative MS-based techniques in combination with traditional virological assays can be used to decipher the role of steady state protein interactions in different steps of the viral life cycle.

TextSentencer_T244

35072-35321

Sentence

denotes

An excellent example is the identification of a PPI network consisting of the HCV receptors CD81 and Claudin1 and the membrane proteins HRas, Rap2B and ITGB1, which are required for efficient entry of the virus into hepatocytes (Zona et al., 2013) .

TextSentencer_T244

35072-35321

Sentence

denotes

An excellent example is the identification of a PPI network consisting of the HCV receptors CD81 and Claudin1 and the membrane proteins HRas, Rap2B and ITGB1, which are required for efficient entry of the virus into hepatocytes (Zona et al., 2013) .

T64338

35072-35321

Sentence

denotes

An excellent example is the identification of a PPI network consisting of the HCV receptors CD81 and Claudin1 and the membrane proteins HRas, Rap2B and ITGB1, which are required for efficient entry of the virus into hepatocytes (Zona et al., 2013) .

TextSentencer_T245

35322-35445

Sentence

denotes

The authors identified the HCV receptor network by SILAC of human hepatoma cells with and without CD81 receptor expression.

TextSentencer_T245

35322-35445

Sentence

denotes

The authors identified the HCV receptor network by SILAC of human hepatoma cells with and without CD81 receptor expression.

T13986

35322-35445

Sentence

denotes

The authors identified the HCV receptor network by SILAC of human hepatoma cells with and without CD81 receptor expression.

TextSentencer_T246

35446-35610

Sentence

denotes

The role of the identified proteins in the HCV entry process was then studied by virological assays in conjunction with RNA silencing and small molecule inhibitors.

TextSentencer_T246

35446-35610

Sentence

denotes

The role of the identified proteins in the HCV entry process was then studied by virological assays in conjunction with RNA silencing and small molecule inhibitors.

T51342

35446-35610

Sentence

denotes

The role of the identified proteins in the HCV entry process was then studied by virological assays in conjunction with RNA silencing and small molecule inhibitors.

TextSentencer_T247

35611-35689

Sentence

denotes

Using a similar workflow, host restriction factors can likewise be discovered.

TextSentencer_T247

35611-35689

Sentence

denotes

Using a similar workflow, host restriction factors can likewise be discovered.

T17570

35611-35689

Sentence

denotes

Using a similar workflow, host restriction factors can likewise be discovered.

TextSentencer_T248

35690-35757

Sentence

denotes

One example is the association of EWI-2 and ␣-actinin-4 in T-cells.

TextSentencer_T248

35690-35757

Sentence

denotes

One example is the association of EWI-2 and ␣-actinin-4 in T-cells.

T77397

35690-35757

Sentence

denotes

One example is the association of EWI-2 and ␣-actinin-4 in T-cells.

TextSentencer_T249

35758-35948

Sentence

denotes

Gordon-Alonso et al. (2012) identified the complex by analyzing EWI-2 co-precipitated proteins via non-quantitative MS, and later on showed that the complex negatively regulates HIV 1 entry.

TextSentencer_T249

35758-35948

Sentence

denotes

Gordon-Alonso et al. (2012) identified the complex by analyzing EWI-2 co-precipitated proteins via non-quantitative MS, and later on showed that the complex negatively regulates HIV 1 entry.

T55612

35758-35948

Sentence

denotes

Gordon-Alonso et al. (2012) identified the complex by analyzing EWI-2 co-precipitated proteins via non-quantitative MS, and later on showed that the complex negatively regulates HIV 1 entry.

TextSentencer_T250

35949-36117

Sentence

denotes

Similarly, the cleavage product of EWI-2, EWI-2wint, has been shown to interact with the HCV receptor CD81 and by this inhibit HCV entry (Rocha-Perugini et al., 2008) .

TextSentencer_T250

35949-36117

Sentence

denotes

Similarly, the cleavage product of EWI-2, EWI-2wint, has been shown to interact with the HCV receptor CD81 and by this inhibit HCV entry (Rocha-Perugini et al., 2008) .

T21740

35949-36117

Sentence

denotes

Similarly, the cleavage product of EWI-2, EWI-2wint, has been shown to interact with the HCV receptor CD81 and by this inhibit HCV entry (Rocha-Perugini et al., 2008) .

TextSentencer_T251

36118-36261

Sentence

denotes

As EWI-2wint is not expressed in the target cells of HCV, which are hepatic cells, this interaction could contribute to the viral cell tropism.

TextSentencer_T251

36118-36261

Sentence

denotes

As EWI-2wint is not expressed in the target cells of HCV, which are hepatic cells, this interaction could contribute to the viral cell tropism.

T42815

36118-36261

Sentence

denotes

As EWI-2wint is not expressed in the target cells of HCV, which are hepatic cells, this interaction could contribute to the viral cell tropism.

TextSentencer_T252

36262-36444

Sentence

denotes

In summary, the analysis of steady state virus receptor interactions can reveal protein complexes critical for virus uptake and in some cases help understand host and tissue tropism.

TextSentencer_T252

36262-36444

Sentence

denotes

In summary, the analysis of steady state virus receptor interactions can reveal protein complexes critical for virus uptake and in some cases help understand host and tissue tropism.

T6355

36262-36444

Sentence

denotes

In summary, the analysis of steady state virus receptor interactions can reveal protein complexes critical for virus uptake and in some cases help understand host and tissue tropism.

TextSentencer_T253

36445-36564

Sentence

denotes

Upon binding of viruses to their receptors, additional secondary PPIs are triggered, most of which lead to virus entry.

TextSentencer_T253

36445-36564

Sentence

denotes

Upon binding of viruses to their receptors, additional secondary PPIs are triggered, most of which lead to virus entry.

T13081

36445-36564

Sentence

denotes

Upon binding of viruses to their receptors, additional secondary PPIs are triggered, most of which lead to virus entry.

TextSentencer_T254

36565-36660

Sentence

denotes

These interactions have at least five distinct functions depending on the virus entry strategy.

TextSentencer_T254

36565-36660

Sentence

denotes

These interactions have at least five distinct functions depending on the virus entry strategy.

T23663

36565-36660

Sentence

denotes

These interactions have at least five distinct functions depending on the virus entry strategy.

TextSentencer_T255

36661-36868

Sentence

denotes

First, binding of the multivalent virus particle to the cell surface can induce receptor clustering, as has been shown for phleboviruses and influenza A viruses (Eierhoff et al., 2010; Lozach et al., 2011) .

TextSentencer_T255

36661-36868

Sentence

denotes

First, binding of the multivalent virus particle to the cell surface can induce receptor clustering, as has been shown for phleboviruses and influenza A viruses (Eierhoff et al., 2010; Lozach et al., 2011) .

T60271

36661-36868

Sentence

denotes

First, binding of the multivalent virus particle to the cell surface can induce receptor clustering, as has been shown for phleboviruses and influenza A viruses (Eierhoff et al., 2010; Lozach et al., 2011) .

TextSentencer_T256

36869-37123

Sentence

denotes

While it is unclear whether influenza A virus triggered clustering of sialylated receptor tyrosine kinases like EGFR and c-Met is required for endocytic virus uptake, phlebovirus induced clustering of DC-SIGN seems to trigger signaling needed for uptake.

TextSentencer_T256

36869-37123

Sentence

denotes

While it is unclear whether influenza A virus triggered clustering of sialylated receptor tyrosine kinases like EGFR and c-Met is required for endocytic virus uptake, phlebovirus induced clustering of DC-SIGN seems to trigger signaling needed for uptake.

T26829

36869-37123

Sentence

denotes

While it is unclear whether influenza A virus triggered clustering of sialylated receptor tyrosine kinases like EGFR and c-Met is required for endocytic virus uptake, phlebovirus induced clustering of DC-SIGN seems to trigger signaling needed for uptake.

TextSentencer_T257

37124-37286

Sentence

denotes

Other viruses, which have been suggested to induce receptor clustering, include coxsackievirus B and Lassa virus (Coyne and Bergelson, 2006; Moraz et al., 2013) .

TextSentencer_T257

37124-37286

Sentence

denotes

Other viruses, which have been suggested to induce receptor clustering, include coxsackievirus B and Lassa virus (Coyne and Bergelson, 2006; Moraz et al., 2013) .

T66571

37124-37286

Sentence

denotes

Other viruses, which have been suggested to induce receptor clustering, include coxsackievirus B and Lassa virus (Coyne and Bergelson, 2006; Moraz et al., 2013) .

TextSentencer_T258

37287-37379

Sentence

denotes

HIV-1 entry also relies on clustering of its CD4 and CXCR4 receptors on the plasma membrane.

TextSentencer_T258

37287-37379

Sentence

denotes

HIV-1 entry also relies on clustering of its CD4 and CXCR4 receptors on the plasma membrane.

T12139

37287-37379

Sentence

denotes

HIV-1 entry also relies on clustering of its CD4 and CXCR4 receptors on the plasma membrane.

TextSentencer_T259

37380-37615

Sentence

denotes

Specifically, the HIV gp120 glycoprotein signals for recruitment of actin adaptor proteins filamin and debrin, which regulate actin rich cap formation at the virus entry site (Gordon-Alonso et al., 2013; Jimenez-Baranda et al., 2007) .

TextSentencer_T259

37380-37615

Sentence

denotes

Specifically, the HIV gp120 glycoprotein signals for recruitment of actin adaptor proteins filamin and debrin, which regulate actin rich cap formation at the virus entry site (Gordon-Alonso et al., 2013; Jimenez-Baranda et al., 2007) .

T12422

37380-37615

Sentence

denotes

Specifically, the HIV gp120 glycoprotein signals for recruitment of actin adaptor proteins filamin and debrin, which regulate actin rich cap formation at the virus entry site (Gordon-Alonso et al., 2013; Jimenez-Baranda et al., 2007) .

TextSentencer_T260

37616-37795

Sentence

denotes

Notably, actin depolymerization is induced at later stages of the HIV entry process, highlighting that actin remodeling during virus entry is highly dynamic and tightly regulated.

TextSentencer_T260

37616-37795

Sentence

denotes

Notably, actin depolymerization is induced at later stages of the HIV entry process, highlighting that actin remodeling during virus entry is highly dynamic and tightly regulated.

T20567

37616-37795

Sentence

denotes

Notably, actin depolymerization is induced at later stages of the HIV entry process, highlighting that actin remodeling during virus entry is highly dynamic and tightly regulated.

TextSentencer_T261

37796-38137

Sentence

denotes

While proteomes of detergent resistant membrane microdomains have been determined in naïve and virus replicating cells resulting in the identification of more than 200 proteins (Foster et al., 2003; Xie et al., 2012) , few quantitative proteomics dataset are currently available for receptor platforms upon virus binding to the cell surface.

TextSentencer_T261

37796-38137

Sentence

denotes

While proteomes of detergent resistant membrane microdomains have been determined in naïve and virus replicating cells resulting in the identification of more than 200 proteins (Foster et al., 2003; Xie et al., 2012) , few quantitative proteomics dataset are currently available for receptor platforms upon virus binding to the cell surface.

T21155

37796-38137

Sentence

denotes

While proteomes of detergent resistant membrane microdomains have been determined in naïve and virus replicating cells resulting in the identification of more than 200 proteins (Foster et al., 2003; Xie et al., 2012) , few quantitative proteomics dataset are currently available for receptor platforms upon virus binding to the cell surface.

TextSentencer_T262

38138-38345

Sentence

denotes

For the HCV receptor CD81, we recently described the virus triggered receptor interactome and identified cytoskeleton regulators, cell junction proteins and a clathrin adaptor protein (Gerold et al., 2015) .

TextSentencer_T262

38138-38345

Sentence

denotes

For the HCV receptor CD81, we recently described the virus triggered receptor interactome and identified cytoskeleton regulators, cell junction proteins and a clathrin adaptor protein (Gerold et al., 2015) .

T71823

38138-38345

Sentence

denotes

For the HCV receptor CD81, we recently described the virus triggered receptor interactome and identified cytoskeleton regulators, cell junction proteins and a clathrin adaptor protein (Gerold et al., 2015) .

TextSentencer_T263

38346-38419

Sentence

denotes

Second, viruses can induce signaling leading to actin cortex disassembly.

TextSentencer_T263

38346-38419

Sentence

denotes

Second, viruses can induce signaling leading to actin cortex disassembly.

T14215

38346-38419

Sentence

denotes

Second, viruses can induce signaling leading to actin cortex disassembly.

TextSentencer_T264

38420-38583

Sentence

denotes

This is particularly important for viruses, which directly penetrate the cell at the plasma membrane and need to overcome the physical barrier of the actin cortex.

TextSentencer_T264

38420-38583

Sentence

denotes

This is particularly important for viruses, which directly penetrate the cell at the plasma membrane and need to overcome the physical barrier of the actin cortex.

T66456

38420-38583

Sentence

denotes

This is particularly important for viruses, which directly penetrate the cell at the plasma membrane and need to overcome the physical barrier of the actin cortex.

TextSentencer_T265

38584-38707

Sentence

denotes

Viruses entering by endocytosis might similarly require local actin cortex disassembly at the site of the incoming vesicle.

TextSentencer_T265

38584-38707

Sentence

denotes

Viruses entering by endocytosis might similarly require local actin cortex disassembly at the site of the incoming vesicle.

T73622

38584-38707

Sentence

denotes

Viruses entering by endocytosis might similarly require local actin cortex disassembly at the site of the incoming vesicle.

TextSentencer_T266

38708-38922

Sentence

denotes

Although the concept that the cortex can prevent or delay transit of viruses has already been suggested by colleagues in 1997 (Marsh and Bron, 1997) , only few studies address virus induced actin cortex remodeling.

TextSentencer_T266

38708-38922

Sentence

denotes

Although the concept that the cortex can prevent or delay transit of viruses has already been suggested by colleagues in 1997 (Marsh and Bron, 1997) , only few studies address virus induced actin cortex remodeling.

T3508

38708-38922

Sentence

denotes

Although the concept that the cortex can prevent or delay transit of viruses has already been suggested by colleagues in 1997 (Marsh and Bron, 1997) , only few studies address virus induced actin cortex remodeling.

TextSentencer_T267

38923-39178

Sentence

denotes

A well-studied example is HIV, which upon Env binding to the CXCR4 coreceptor induces Galpha i signaling and subsequent cofilin activation leading to actin depolymerization thereby facilitating nuclear translocation of HIV particles (Yoder et al., 2008) .

TextSentencer_T267

38923-39178

Sentence

denotes

A well-studied example is HIV, which upon Env binding to the CXCR4 coreceptor induces Galpha i signaling and subsequent cofilin activation leading to actin depolymerization thereby facilitating nuclear translocation of HIV particles (Yoder et al., 2008) .

T89708

38923-39178

Sentence

denotes

A well-studied example is HIV, which upon Env binding to the CXCR4 coreceptor induces Galpha i signaling and subsequent cofilin activation leading to actin depolymerization thereby facilitating nuclear translocation of HIV particles (Yoder et al., 2008) .

TextSentencer_T268

39179-39269

Sentence

denotes

Of note, not only actin cortex but also actin stress fiber disruption can aid virus entry.

TextSentencer_T268

39179-39269

Sentence

denotes

Of note, not only actin cortex but also actin stress fiber disruption can aid virus entry.

T52879

39179-39269

Sentence

denotes

Of note, not only actin cortex but also actin stress fiber disruption can aid virus entry.

TextSentencer_T269

39270-39483

Sentence

denotes

For instance cytomegaloviruses binding to EGFR and integrin alphaVbeta3, induces cofilin dependent actin stress fiber disruption thereby facilitating nuclear translocation of incoming virions (Wang et al., 2005) .

TextSentencer_T269

39270-39483

Sentence

denotes

For instance cytomegaloviruses binding to EGFR and integrin alphaVbeta3, induces cofilin dependent actin stress fiber disruption thereby facilitating nuclear translocation of incoming virions (Wang et al., 2005) .

T965

39270-39483

Sentence

denotes

For instance cytomegaloviruses binding to EGFR and integrin alphaVbeta3, induces cofilin dependent actin stress fiber disruption thereby facilitating nuclear translocation of incoming virions (Wang et al., 2005) .

TextSentencer_T270

39484-39642

Sentence

denotes

Third, viruses, which use multiple receptors for entry, can induce their lateral translocation along the plasma membrane towards the site of endocytic uptake.

TextSentencer_T270

39484-39642

Sentence

denotes

Third, viruses, which use multiple receptors for entry, can induce their lateral translocation along the plasma membrane towards the site of endocytic uptake.

T4862

39484-39642

Sentence

denotes

Third, viruses, which use multiple receptors for entry, can induce their lateral translocation along the plasma membrane towards the site of endocytic uptake.

TextSentencer_T271

39643-39865

Sentence

denotes

A prominent example of such surfing is coxsackievirus B, which after binding to the apical decay-accelerating factor (DAF) on epithelial cells induces Abl kinase signaling and subsequent Rac-dependent actin reorganization.

TextSentencer_T271

39643-39865

Sentence

denotes

A prominent example of such surfing is coxsackievirus B, which after binding to the apical decay-accelerating factor (DAF) on epithelial cells induces Abl kinase signaling and subsequent Rac-dependent actin reorganization.

T28194

39643-39865

Sentence

denotes

A prominent example of such surfing is coxsackievirus B, which after binding to the apical decay-accelerating factor (DAF) on epithelial cells induces Abl kinase signaling and subsequent Rac-dependent actin reorganization.

TextSentencer_T272

39866-40045

Sentence

denotes

This leads to the lateral translocation of the coxsackievirus B-DAF complex to tight junctions, where the secondary receptor coxsackievirus-adenovirus receptor (CAR) is localized.

TextSentencer_T272

39866-40045

Sentence

denotes

This leads to the lateral translocation of the coxsackievirus B-DAF complex to tight junctions, where the secondary receptor coxsackievirus-adenovirus receptor (CAR) is localized.

T9446

39866-40045

Sentence

denotes

This leads to the lateral translocation of the coxsackievirus B-DAF complex to tight junctions, where the secondary receptor coxsackievirus-adenovirus receptor (CAR) is localized.

TextSentencer_T273

40046-40099

Sentence

denotes

After CAR engagement coxsackievirus B is endocytosed.

TextSentencer_T273

40046-40099

Sentence

denotes

After CAR engagement coxsackievirus B is endocytosed.

T16810

40046-40099

Sentence

denotes

After CAR engagement coxsackievirus B is endocytosed.

TextSentencer_T274

40100-40286

Sentence

denotes

This endocytosis is also triggered by PPIs as initial DAF binding additionally induces Fyn kinase, which phosphorylates caveolin thereby facilitating uptake (Coyne and Bergelson, 2006) .

TextSentencer_T274

40100-40286

Sentence

denotes

This endocytosis is also triggered by PPIs as initial DAF binding additionally induces Fyn kinase, which phosphorylates caveolin thereby facilitating uptake (Coyne and Bergelson, 2006) .

T89677

40100-40286

Sentence

denotes

This endocytosis is also triggered by PPIs as initial DAF binding additionally induces Fyn kinase, which phosphorylates caveolin thereby facilitating uptake (Coyne and Bergelson, 2006) .

TextSentencer_T275

40287-40446

Sentence

denotes

HCV seems to use a similar multistep strategy to enter after initial binding to the basolateral side of hepatocytes, where the receptors SR-BI and CD81 reside.

TextSentencer_T275

40287-40446

Sentence

denotes

HCV seems to use a similar multistep strategy to enter after initial binding to the basolateral side of hepatocytes, where the receptors SR-BI and CD81 reside.

T86805

40287-40446

Sentence

denotes

HCV seems to use a similar multistep strategy to enter after initial binding to the basolateral side of hepatocytes, where the receptors SR-BI and CD81 reside.

TextSentencer_T276

40447-40691

Sentence

denotes

Through a yet insufficiently described mechanism HCV also triggers lateral translocation of the CD81-virus complex to tight junctions, where the two additional entry factors CLDN1 and OCLN reside and endocytosis occurs (Brazzoli et al., 2008) .

TextSentencer_T276

40447-40691

Sentence

denotes

Through a yet insufficiently described mechanism HCV also triggers lateral translocation of the CD81-virus complex to tight junctions, where the two additional entry factors CLDN1 and OCLN reside and endocytosis occurs (Brazzoli et al., 2008) .

T97252

40447-40691

Sentence

denotes

Through a yet insufficiently described mechanism HCV also triggers lateral translocation of the CD81-virus complex to tight junctions, where the two additional entry factors CLDN1 and OCLN reside and endocytosis occurs (Brazzoli et al., 2008) .

TextSentencer_T277

40692-40842

Sentence

denotes

Receptor tyrosine kinases like EGFR are thought to provide the trigger for lateral membrane translocation through HRas signaling (Zona et al., 2013) .

TextSentencer_T277

40692-40842

Sentence

denotes

Receptor tyrosine kinases like EGFR are thought to provide the trigger for lateral membrane translocation through HRas signaling (Zona et al., 2013) .

T43723

40692-40842

Sentence

denotes

Receptor tyrosine kinases like EGFR are thought to provide the trigger for lateral membrane translocation through HRas signaling (Zona et al., 2013) .

TextSentencer_T278

40843-41011

Sentence

denotes

Moreover, surfing of HCV and retroviruses on filopodia has been observed and is governed by PPI with the actin cell cortex (Coller et al., 2009; Lehmann et al., 2005) .

TextSentencer_T278

40843-41011

Sentence

denotes

Moreover, surfing of HCV and retroviruses on filopodia has been observed and is governed by PPI with the actin cell cortex (Coller et al., 2009; Lehmann et al., 2005) .

T56637

40843-41011

Sentence

denotes

Moreover, surfing of HCV and retroviruses on filopodia has been observed and is governed by PPI with the actin cell cortex (Coller et al., 2009; Lehmann et al., 2005) .

TextSentencer_T279

41012-41290

Sentence

denotes

Fourth, viruses, which enter through endocytic routes, can induce endocytic uptake mechanisms including clathrin-mediated, caveolin-dependent, macropinocytic or alternative uptake routes like the clathrin-independent carriers in parvovirus entry (Nonnenmacher and Weber, 2011) .

TextSentencer_T279

41012-41290

Sentence

denotes

Fourth, viruses, which enter through endocytic routes, can induce endocytic uptake mechanisms including clathrin-mediated, caveolin-dependent, macropinocytic or alternative uptake routes like the clathrin-independent carriers in parvovirus entry (Nonnenmacher and Weber, 2011) .

T24252

41012-41290

Sentence

denotes

Fourth, viruses, which enter through endocytic routes, can induce endocytic uptake mechanisms including clathrin-mediated, caveolin-dependent, macropinocytic or alternative uptake routes like the clathrin-independent carriers in parvovirus entry (Nonnenmacher and Weber, 2011) .

TextSentencer_T280

41291-41422

Sentence

denotes

On the one hand, some viruses like human rhinovirus 2 and phleboviruses hijack endogenous constitutive receptor recycling pathways.

TextSentencer_T280

41291-41422

Sentence

denotes

On the one hand, some viruses like human rhinovirus 2 and phleboviruses hijack endogenous constitutive receptor recycling pathways.

T13164

41291-41422

Sentence

denotes

On the one hand, some viruses like human rhinovirus 2 and phleboviruses hijack endogenous constitutive receptor recycling pathways.

TextSentencer_T281

41423-41637

Sentence

denotes

After endocytosis phleboviruses, which hijack DC-SIGN for cell entry into DCs, however dissociate from the receptor in the early endosome thereby avoiding antigen processing and presentation (Lozach et al., 2011) .

TextSentencer_T281

41423-41637

Sentence

denotes

After endocytosis phleboviruses, which hijack DC-SIGN for cell entry into DCs, however dissociate from the receptor in the early endosome thereby avoiding antigen processing and presentation (Lozach et al., 2011) .

T69786

41423-41637

Sentence

denotes

After endocytosis phleboviruses, which hijack DC-SIGN for cell entry into DCs, however dissociate from the receptor in the early endosome thereby avoiding antigen processing and presentation (Lozach et al., 2011) .

TextSentencer_T282

41638-41727

Sentence

denotes

On the other hand, viruses can actively trigger their endocytosis like influenza A virus.

TextSentencer_T282

41638-41727

Sentence

denotes

On the other hand, viruses can actively trigger their endocytosis like influenza A virus.

T43673

41638-41727

Sentence

denotes

On the other hand, viruses can actively trigger their endocytosis like influenza A virus.

TextSentencer_T283

41728-41964

Sentence

denotes

After interaction of influenza virions with sialylated membrane receptors, the clathrin adaptor Epsin-1 is recruited in a ubiquitin-dependent manner towards the receptor complex and induces clathrin-coated pits (Chen and Zhuang, 2008) .

TextSentencer_T283

41728-41964

Sentence

denotes

After interaction of influenza virions with sialylated membrane receptors, the clathrin adaptor Epsin-1 is recruited in a ubiquitin-dependent manner towards the receptor complex and induces clathrin-coated pits (Chen and Zhuang, 2008) .

T1152

41728-41964

Sentence

denotes

After interaction of influenza virions with sialylated membrane receptors, the clathrin adaptor Epsin-1 is recruited in a ubiquitin-dependent manner towards the receptor complex and induces clathrin-coated pits (Chen and Zhuang, 2008) .

TextSentencer_T284

41965-42117

Sentence

denotes

PI3K activation was independently reported to be required for influenza uptake, thus more than one signaling pathway might coordinate uptake of a virus.

TextSentencer_T284

41965-42117

Sentence

denotes

PI3K activation was independently reported to be required for influenza uptake, thus more than one signaling pathway might coordinate uptake of a virus.

T53092

41965-42117

Sentence

denotes

PI3K activation was independently reported to be required for influenza uptake, thus more than one signaling pathway might coordinate uptake of a virus.

TextSentencer_T285

42118-42296

Sentence

denotes

This is in line with reports, showing that influenza virus can utilize more than one endocytosis pathway to gain access to host cells (Rust et al., 2004; de Vries et al., 2011) .

TextSentencer_T285

42118-42296

Sentence

denotes

This is in line with reports, showing that influenza virus can utilize more than one endocytosis pathway to gain access to host cells (Rust et al., 2004; de Vries et al., 2011) .

T33780

42118-42296

Sentence

denotes

This is in line with reports, showing that influenza virus can utilize more than one endocytosis pathway to gain access to host cells (Rust et al., 2004; de Vries et al., 2011) .

TextSentencer_T286

42297-42499

Sentence

denotes

Larger viruses like poxviruses enter by macropinocytosis and actively induce this uptake pathway through Rac-1 and p21-activated kinase 1 (Pak-1) dependent actin remodeling (Mercer and Helenius, 2008) .

TextSentencer_T286

42297-42499

Sentence

denotes

Larger viruses like poxviruses enter by macropinocytosis and actively induce this uptake pathway through Rac-1 and p21-activated kinase 1 (Pak-1) dependent actin remodeling (Mercer and Helenius, 2008) .

T34143

42297-42499

Sentence

denotes

Larger viruses like poxviruses enter by macropinocytosis and actively induce this uptake pathway through Rac-1 and p21-activated kinase 1 (Pak-1) dependent actin remodeling (Mercer and Helenius, 2008) .

TextSentencer_T287

42500-42727

Sentence

denotes

Formation of plasma membrane protrusions is however not specific to poxviruses, but occurs also during entry of herpes viruses, papillomaviruses and flaviviruses (Clement et al., 2006; Coller et al., 2009; Smith et al., 2008) .

TextSentencer_T287

42500-42727

Sentence

denotes

Formation of plasma membrane protrusions is however not specific to poxviruses, but occurs also during entry of herpes viruses, papillomaviruses and flaviviruses (Clement et al., 2006; Coller et al., 2009; Smith et al., 2008) .

T87966

42500-42727

Sentence

denotes

Formation of plasma membrane protrusions is however not specific to poxviruses, but occurs also during entry of herpes viruses, papillomaviruses and flaviviruses (Clement et al., 2006; Coller et al., 2009; Smith et al., 2008) .

TextSentencer_T288

42728-42811

Sentence

denotes

Lastly, several viruses need to interact with host enzymes to trigger their uptake.

TextSentencer_T288

42728-42811

Sentence

denotes

Lastly, several viruses need to interact with host enzymes to trigger their uptake.

T91292

42728-42811

Sentence

denotes

Lastly, several viruses need to interact with host enzymes to trigger their uptake.

TextSentencer_T289

42812-42995

Sentence

denotes

A prominent example is ebola virus, which requires proteolytic processing of its envelope glycoprotein GP1 by cathepsin B and L to render it fusion competent (Chandran et al., 2005) .

TextSentencer_T289

42812-42995

Sentence

denotes

A prominent example is ebola virus, which requires proteolytic processing of its envelope glycoprotein GP1 by cathepsin B and L to render it fusion competent (Chandran et al., 2005) .

T66484

42812-42995

Sentence

denotes

A prominent example is ebola virus, which requires proteolytic processing of its envelope glycoprotein GP1 by cathepsin B and L to render it fusion competent (Chandran et al., 2005) .

TextSentencer_T290

42996-43109

Sentence

denotes

Similarly coronavirus relies on cathepsin cleavage of its spike protein to permit fusion (Simmons et al., 2005) .

TextSentencer_T290

42996-43109

Sentence

denotes

Similarly coronavirus relies on cathepsin cleavage of its spike protein to permit fusion (Simmons et al., 2005) .

T49980

42996-43109

Sentence

denotes

Similarly coronavirus relies on cathepsin cleavage of its spike protein to permit fusion (Simmons et al., 2005) .

TextSentencer_T291

43110-43307

Sentence

denotes

In addition to lysosomal enzymes, cell surface proteases can prime VAPs for fusion, like shown for some influenza A virus strains and SARS coronavirus (Bertram et al., 2010; Bertram et al., 2011) .

TextSentencer_T291

43110-43307

Sentence

denotes

In addition to lysosomal enzymes, cell surface proteases can prime VAPs for fusion, like shown for some influenza A virus strains and SARS coronavirus (Bertram et al., 2010; Bertram et al., 2011) .

T41322

43110-43307

Sentence

denotes

In addition to lysosomal enzymes, cell surface proteases can prime VAPs for fusion, like shown for some influenza A virus strains and SARS coronavirus (Bertram et al., 2010; Bertram et al., 2011) .

TextSentencer_T292

43308-43582

Sentence

denotes

Host protein disulfide isomerases similarly regulate entry by catalyzing disulfide shuffling in viral envelope proteins, as shown for dengue virus, HIV-1 and Newcastle disease virus (Jain et al., 2008; Ryser et al., 1994; Stantchev et al., 2012; Vega-Almeida et al., 2013) .

TextSentencer_T292

43308-43582

Sentence

denotes

Host protein disulfide isomerases similarly regulate entry by catalyzing disulfide shuffling in viral envelope proteins, as shown for dengue virus, HIV-1 and Newcastle disease virus (Jain et al., 2008; Ryser et al., 1994; Stantchev et al., 2012; Vega-Almeida et al., 2013) .

T83136

43308-43582

Sentence

denotes

Host protein disulfide isomerases similarly regulate entry by catalyzing disulfide shuffling in viral envelope proteins, as shown for dengue virus, HIV-1 and Newcastle disease virus (Jain et al., 2008; Ryser et al., 1994; Stantchev et al., 2012; Vega-Almeida et al., 2013) .

TextSentencer_T293

43583-43781

Sentence

denotes

Of note, high resolution proteomics can not only reveal transient interactions of VAP with enzymes, but also has the potential to identify proteolytic cleavage sites and redox modifications in VAPs.

TextSentencer_T293

43583-43781

Sentence

denotes

Of note, high resolution proteomics can not only reveal transient interactions of VAP with enzymes, but also has the potential to identify proteolytic cleavage sites and redox modifications in VAPs.

T41253

43583-43781

Sentence

denotes

Of note, high resolution proteomics can not only reveal transient interactions of VAP with enzymes, but also has the potential to identify proteolytic cleavage sites and redox modifications in VAPs.

TextSentencer_T294

43782-43964

Sentence

denotes

It is conceivable that virus induced protein interactions during entry not only serve to promote the virus uptake pathway, but can also help cloak viruses and lead to immune evasion.

TextSentencer_T294

43782-43964

Sentence

denotes

It is conceivable that virus induced protein interactions during entry not only serve to promote the virus uptake pathway, but can also help cloak viruses and lead to immune evasion.

T4168

43782-43964

Sentence

denotes

It is conceivable that virus induced protein interactions during entry not only serve to promote the virus uptake pathway, but can also help cloak viruses and lead to immune evasion.

TextSentencer_T295

43965-44189

Sentence

denotes

For instance, the HIV capsid recruits two cofactors, cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), thereby preventing antiviral IFN responses (Rasaiyaah et al., 2013) .

TextSentencer_T295

43965-44189

Sentence

denotes

For instance, the HIV capsid recruits two cofactors, cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), thereby preventing antiviral IFN responses (Rasaiyaah et al., 2013) .

T66359

43965-44189

Sentence

denotes

For instance, the HIV capsid recruits two cofactors, cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), thereby preventing antiviral IFN responses (Rasaiyaah et al., 2013) .

TextSentencer_T296

44190-44348

Sentence

denotes

More complex viruses can further express viral gene products on the infected cell surface, which then bind receptors on bystander cells and modulate immunity.

TextSentencer_T296

44190-44348

Sentence

denotes

More complex viruses can further express viral gene products on the infected cell surface, which then bind receptors on bystander cells and modulate immunity.

T14320

44190-44348

Sentence

denotes

More complex viruses can further express viral gene products on the infected cell surface, which then bind receptors on bystander cells and modulate immunity.

TextSentencer_T297

44349-44468

Sentence

denotes

For instance, HCMV protein pUL11 binds to CD45 on T cells thereby reducing T cell proliferation (Gabaev et al., 2011) .

TextSentencer_T297

44349-44468

Sentence

denotes

For instance, HCMV protein pUL11 binds to CD45 on T cells thereby reducing T cell proliferation (Gabaev et al., 2011) .

T27068

44349-44468

Sentence

denotes

For instance, HCMV protein pUL11 binds to CD45 on T cells thereby reducing T cell proliferation (Gabaev et al., 2011) .

TextSentencer_T298

44469-44663

Sentence

denotes

While we here focus on the role of virus -host PPI in entry, it should be noted that quantitative virus entry proteomics at the same time has the potential to reveal immunomodulatory mechanisms.

TextSentencer_T298

44469-44663

Sentence

denotes

While we here focus on the role of virus -host PPI in entry, it should be noted that quantitative virus entry proteomics at the same time has the potential to reveal immunomodulatory mechanisms.

T64938

44469-44663

Sentence

denotes

While we here focus on the role of virus -host PPI in entry, it should be noted that quantitative virus entry proteomics at the same time has the potential to reveal immunomodulatory mechanisms.

TextSentencer_T299

44664-44809

Sentence

denotes

Similarly, PPIs of viral tegument and capsid proteins with host proteins occurring after membrane fusion are amenable to quantitative proteomics.

TextSentencer_T299

44664-44809

Sentence

denotes

Similarly, PPIs of viral tegument and capsid proteins with host proteins occurring after membrane fusion are amenable to quantitative proteomics.

T10368

44664-44809

Sentence

denotes

Similarly, PPIs of viral tegument and capsid proteins with host proteins occurring after membrane fusion are amenable to quantitative proteomics.

TextSentencer_T300

44810-44969

Sentence

denotes

We refer the reader elsewhere for the detailed description of post-fusion PPIs coordinating nuclear trafficking (Dohner et al., 2005; Yarbrough et al., 2014) .

TextSentencer_T300

44810-44969

Sentence

denotes

We refer the reader elsewhere for the detailed description of post-fusion PPIs coordinating nuclear trafficking (Dohner et al., 2005; Yarbrough et al., 2014) .

T92269

44810-44969

Sentence

denotes

We refer the reader elsewhere for the detailed description of post-fusion PPIs coordinating nuclear trafficking (Dohner et al., 2005; Yarbrough et al., 2014) .

TextSentencer_T301

44970-45106

Sentence

denotes

Comprehensive proteomics analyses of virus induced PPIs leading to actin remodeling and endocytic uptake of virions are lacking to date.

TextSentencer_T301

44970-45106

Sentence

denotes

Comprehensive proteomics analyses of virus induced PPIs leading to actin remodeling and endocytic uptake of virions are lacking to date.

T77448

44970-45106

Sentence

denotes

Comprehensive proteomics analyses of virus induced PPIs leading to actin remodeling and endocytic uptake of virions are lacking to date.

TextSentencer_T302

45107-45239

Sentence

denotes

However, several studies underline the value of proteomics to analyze stimulus specific interactions in cellular signaling pathways.

TextSentencer_T302

45107-45239

Sentence

denotes

However, several studies underline the value of proteomics to analyze stimulus specific interactions in cellular signaling pathways.

T98734

45107-45239

Sentence

denotes

However, several studies underline the value of proteomics to analyze stimulus specific interactions in cellular signaling pathways.

TextSentencer_T303

45240-45463

Sentence

denotes

For instance, the ligand-induced changes of the two Wnt signaling pathway members adenomatous polyposis coli protein (APC) and axin-1 identified 28 and 18 dynamic interaction partners, respectively (Hilger and Mann, 2012) .

TextSentencer_T303

45240-45463

Sentence

denotes

For instance, the ligand-induced changes of the two Wnt signaling pathway members adenomatous polyposis coli protein (APC) and axin-1 identified 28 and 18 dynamic interaction partners, respectively (Hilger and Mann, 2012) .

T25530

45240-45463

Sentence

denotes

For instance, the ligand-induced changes of the two Wnt signaling pathway members adenomatous polyposis coli protein (APC) and axin-1 identified 28 and 18 dynamic interaction partners, respectively (Hilger and Mann, 2012) .

TextSentencer_T304

45464-45620

Sentence

denotes

For other virus life cycle steps, like e.g., CMV particle assembly, interaction proteomics uncovered important mechanistic insights (Moorman et al., 2010) .

TextSentencer_T304

45464-45620

Sentence

denotes

For other virus life cycle steps, like e.g., CMV particle assembly, interaction proteomics uncovered important mechanistic insights (Moorman et al., 2010) .

T96783

45464-45620

Sentence

denotes

For other virus life cycle steps, like e.g., CMV particle assembly, interaction proteomics uncovered important mechanistic insights (Moorman et al., 2010) .

TextSentencer_T305

45621-45832

Sentence

denotes

Further, interaction proteomics of viral immunomodulatory proteins revealed virus induced alterations in human protein interaction networks and underlying viral perturbation strategies (Pichlmair et al., 2012) .

TextSentencer_T305

45621-45832

Sentence

denotes

Further, interaction proteomics of viral immunomodulatory proteins revealed virus induced alterations in human protein interaction networks and underlying viral perturbation strategies (Pichlmair et al., 2012) .

T85024

45621-45832

Sentence

denotes

Further, interaction proteomics of viral immunomodulatory proteins revealed virus induced alterations in human protein interaction networks and underlying viral perturbation strategies (Pichlmair et al., 2012) .

TextSentencer_T306

45833-45976

Sentence

denotes

Similar studies hold the promise of uncovering common and specific viral strategies to alter and exploit host cell functions during cell entry.

TextSentencer_T306

45833-45976

Sentence

denotes

Similar studies hold the promise of uncovering common and specific viral strategies to alter and exploit host cell functions during cell entry.

T11193

45833-45976

Sentence

denotes

Similar studies hold the promise of uncovering common and specific viral strategies to alter and exploit host cell functions during cell entry.

TextSentencer_T307

45977-46074

Sentence

denotes

Post-translational modifications (PTMs) play two major roles during virus entry into a host cell.

TextSentencer_T307

45977-46074

Sentence

denotes

Post-translational modifications (PTMs) play two major roles during virus entry into a host cell.

T69983

45977-46074

Sentence

denotes

Post-translational modifications (PTMs) play two major roles during virus entry into a host cell.

TextSentencer_T308

46075-46173

Sentence

denotes

First, virus receptor PTMs can be critical for the localization to specific membrane microdomains.

TextSentencer_T308

46075-46173

Sentence

denotes

First, virus receptor PTMs can be critical for the localization to specific membrane microdomains.

T92742

46075-46173

Sentence

denotes

First, virus receptor PTMs can be critical for the localization to specific membrane microdomains.

TextSentencer_T309

46174-46453

Sentence

denotes

For instance, palmitoylation of the HCV receptor CD81 and its associated proteins EWI-2 and EWI-2wint regulate their interaction with each other and the localization to cholesterol rich membrane domains thereby influencing HCV entry (Montpellier et al., 2011; Zhu et al., 2012) .

TextSentencer_T309

46174-46453

Sentence

denotes

For instance, palmitoylation of the HCV receptor CD81 and its associated proteins EWI-2 and EWI-2wint regulate their interaction with each other and the localization to cholesterol rich membrane domains thereby influencing HCV entry (Montpellier et al., 2011; Zhu et al., 2012) .

T39886

46174-46453

Sentence

denotes

For instance, palmitoylation of the HCV receptor CD81 and its associated proteins EWI-2 and EWI-2wint regulate their interaction with each other and the localization to cholesterol rich membrane domains thereby influencing HCV entry (Montpellier et al., 2011; Zhu et al., 2012) .

TextSentencer_T310

46454-46607

Sentence

denotes

Second, viruses rely on cell signaling for their uptake and such cellular signals are often transmitted via PTMs like reversible protein phosphorylation.

TextSentencer_T310

46454-46607

Sentence

denotes

Second, viruses rely on cell signaling for their uptake and such cellular signals are often transmitted via PTMs like reversible protein phosphorylation.

T72157

46454-46607

Sentence

denotes

Second, viruses rely on cell signaling for their uptake and such cellular signals are often transmitted via PTMs like reversible protein phosphorylation.

TextSentencer_T311

46608-46872

Sentence

denotes

A widespread example common to viruses of diverse families including herpesviruses, papillomaviruses and flaviviruses is the triggering of receptor tyrosine kinase signaling (Hahn et al., 2012; Lupberger et al., 2011; Surviladze et al., 2013; Zheng et al., 2014) .

TextSentencer_T311

46608-46872

Sentence

denotes

A widespread example common to viruses of diverse families including herpesviruses, papillomaviruses and flaviviruses is the triggering of receptor tyrosine kinase signaling (Hahn et al., 2012; Lupberger et al., 2011; Surviladze et al., 2013; Zheng et al., 2014) .

T98486

46608-46872

Sentence

denotes

A widespread example common to viruses of diverse families including herpesviruses, papillomaviruses and flaviviruses is the triggering of receptor tyrosine kinase signaling (Hahn et al., 2012; Lupberger et al., 2011; Surviladze et al., 2013; Zheng et al., 2014) .

TextSentencer_T312

46873-46999

Sentence

denotes

In most cases signaling through growth factor receptors regulates actin dynamics required for virus trafficking into the cell.

TextSentencer_T312

46873-46999

Sentence

denotes

In most cases signaling through growth factor receptors regulates actin dynamics required for virus trafficking into the cell.

T37350

46873-46999

Sentence

denotes

In most cases signaling through growth factor receptors regulates actin dynamics required for virus trafficking into the cell.

TextSentencer_T313

47000-47130

Sentence

denotes

Some respiratory viruses however use EGFR signaling to suppress antiviral signaling in the airway epithelium (Ueki et al., 2013) .

TextSentencer_T313

47000-47130

Sentence

denotes

Some respiratory viruses however use EGFR signaling to suppress antiviral signaling in the airway epithelium (Ueki et al., 2013) .

T47931

47000-47130

Sentence

denotes

Some respiratory viruses however use EGFR signaling to suppress antiviral signaling in the airway epithelium (Ueki et al., 2013) .

TextSentencer_T314

47131-47355

Sentence

denotes

Other phosphorylation signals that coordinate virus entry are the Src kinase pathway in HCMV penetration (Nogalski et al., 2013) and the Lassa virus induced phosphorylation of its receptor dystroglycan (Moraz et al., 2013) .

TextSentencer_T314

47131-47355

Sentence

denotes

Other phosphorylation signals that coordinate virus entry are the Src kinase pathway in HCMV penetration (Nogalski et al., 2013) and the Lassa virus induced phosphorylation of its receptor dystroglycan (Moraz et al., 2013) .

T59532

47131-47355

Sentence

denotes

Other phosphorylation signals that coordinate virus entry are the Src kinase pathway in HCMV penetration (Nogalski et al., 2013) and the Lassa virus induced phosphorylation of its receptor dystroglycan (Moraz et al., 2013) .

TextSentencer_T315

47356-47507

Sentence

denotes

Certain kinase activities can be a hallmark of a specific uptake pathway, as for instance PAK-1 for macropinocytic virus entry (Amstutz et al., 2008) .

TextSentencer_T315

47356-47507

Sentence

denotes

Certain kinase activities can be a hallmark of a specific uptake pathway, as for instance PAK-1 for macropinocytic virus entry (Amstutz et al., 2008) .

T14910

47356-47507

Sentence

denotes

Certain kinase activities can be a hallmark of a specific uptake pathway, as for instance PAK-1 for macropinocytic virus entry (Amstutz et al., 2008) .

TextSentencer_T316

47508-47645

Sentence

denotes

In particular for large DNA viruses not only host proteins are phosphorylated early during virus infection, but also viral gene products.

TextSentencer_T316

47508-47645

Sentence

denotes

In particular for large DNA viruses not only host proteins are phosphorylated early during virus infection, but also viral gene products.

T84309

47508-47645

Sentence

denotes

In particular for large DNA viruses not only host proteins are phosphorylated early during virus infection, but also viral gene products.

TextSentencer_T317

47646-47884

Sentence

denotes

For instance, herpes simplex virus type 1 (HSV-1) protein pUL46 is heavily phosphorylated six hours post infection and interacts with several viral and host kinases as determined by quantitative interaction proteomics (Lin et al., 2013) .

TextSentencer_T317

47646-47884

Sentence

denotes

For instance, herpes simplex virus type 1 (HSV-1) protein pUL46 is heavily phosphorylated six hours post infection and interacts with several viral and host kinases as determined by quantitative interaction proteomics (Lin et al., 2013) .

T67668

47646-47884

Sentence

denotes

For instance, herpes simplex virus type 1 (HSV-1) protein pUL46 is heavily phosphorylated six hours post infection and interacts with several viral and host kinases as determined by quantitative interaction proteomics (Lin et al., 2013) .

TextSentencer_T318

47885-48019

Sentence

denotes

Apart from protein phosphorylation, other PTMs like ubiquitination are thought to regulate virus uptake, but are poorly characterized.

TextSentencer_T318

47885-48019

Sentence

denotes

Apart from protein phosphorylation, other PTMs like ubiquitination are thought to regulate virus uptake, but are poorly characterized.

T81056

47885-48019

Sentence

denotes

Apart from protein phosphorylation, other PTMs like ubiquitination are thought to regulate virus uptake, but are poorly characterized.

TextSentencer_T319

48020-48111

Sentence

denotes

Ubiquitination of viral proteins seems to induce viral uncoating in at least two instances.

TextSentencer_T319

48020-48111

Sentence

denotes

Ubiquitination of viral proteins seems to induce viral uncoating in at least two instances.

T87803

48020-48111

Sentence

denotes

Ubiquitination of viral proteins seems to induce viral uncoating in at least two instances.

TextSentencer_T320

48112-48247

Sentence

denotes

Influenza A virus M1 protein is ubiquitinated by the E3 ligase Itch and this is a prerequisite for endosomal escape (Su et al., 2013) .

TextSentencer_T320

48112-48247

Sentence

denotes

Influenza A virus M1 protein is ubiquitinated by the E3 ligase Itch and this is a prerequisite for endosomal escape (Su et al., 2013) .

T43388

48112-48247

Sentence

denotes

Influenza A virus M1 protein is ubiquitinated by the E3 ligase Itch and this is a prerequisite for endosomal escape (Su et al., 2013) .

TextSentencer_T321

48248-48385

Sentence

denotes

Vaccinia virus on the other hand uses ubiquitinated incoming viral core proteins to trigger proteasomal degradation of its protein coat .

TextSentencer_T321

48248-48385

Sentence

denotes

Vaccinia virus on the other hand uses ubiquitinated incoming viral core proteins to trigger proteasomal degradation of its protein coat .

T24522

48248-48385

Sentence

denotes

Vaccinia virus on the other hand uses ubiquitinated incoming viral core proteins to trigger proteasomal degradation of its protein coat .

TextSentencer_T322

48386-48598

Sentence

denotes

All aforementioned studies, except for the HSV-1 study, demonstrate PTMs of receptors, downstream signaling molecules or viral proteins by immunoblotting, thus requiring prior knowledge of the signaling pathways.

TextSentencer_T322

48386-48598

Sentence

denotes

All aforementioned studies, except for the HSV-1 study, demonstrate PTMs of receptors, downstream signaling molecules or viral proteins by immunoblotting, thus requiring prior knowledge of the signaling pathways.

T90262

48386-48598

Sentence

denotes

All aforementioned studies, except for the HSV-1 study, demonstrate PTMs of receptors, downstream signaling molecules or viral proteins by immunoblotting, thus requiring prior knowledge of the signaling pathways.

TextSentencer_T323

48599-48748

Sentence

denotes

In contrast, MS-based identification and quantification of PTMs upon virus binding to a host cell is completely unbiased and thus broadly applicable.

TextSentencer_T323

48599-48748

Sentence

denotes

In contrast, MS-based identification and quantification of PTMs upon virus binding to a host cell is completely unbiased and thus broadly applicable.

T32812

48599-48748

Sentence

denotes

In contrast, MS-based identification and quantification of PTMs upon virus binding to a host cell is completely unbiased and thus broadly applicable.

TextSentencer_T324

48749-48931

Sentence

denotes

Another advantage over previous immunoblot based methods is the global and quantitative measurement of PTMs by MS in conjunction with the ability to pinpoint the modified amino acid.

TextSentencer_T324

48749-48931

Sentence

denotes

Another advantage over previous immunoblot based methods is the global and quantitative measurement of PTMs by MS in conjunction with the ability to pinpoint the modified amino acid.

T10926

48749-48931

Sentence

denotes

Another advantage over previous immunoblot based methods is the global and quantitative measurement of PTMs by MS in conjunction with the ability to pinpoint the modified amino acid.

TextSentencer_T325

48932-49115

Sentence

denotes

Clearly, high read depth is required for PTM proteomics as the search space for the peptides explodes when taking into account all possible peptide PTMs and all of their combinations.

TextSentencer_T325

48932-49115

Sentence

denotes

Clearly, high read depth is required for PTM proteomics as the search space for the peptides explodes when taking into account all possible peptide PTMs and all of their combinations.

T67453

48932-49115

Sentence

denotes

Clearly, high read depth is required for PTM proteomics as the search space for the peptides explodes when taking into account all possible peptide PTMs and all of their combinations.

TextSentencer_T326

49116-49457

Sentence

denotes

Still successful large-scale measurements of protein phosphorylation (Ficarro et al., 2002; Olsen et al., 2006) , N-glycosylation (Kaji et al., 2007) , lysine methylation (Ong et al., 2004) or acetylation (Kim et al., 2006) , ubiquitination (Peng et al., 2003) and sumoylation (Andersen et al., 2009; Impens et al., 2014) have been achieved.

TextSentencer_T326

49116-49457

Sentence

denotes

Still successful large-scale measurements of protein phosphorylation (Ficarro et al., 2002; Olsen et al., 2006) , N-glycosylation (Kaji et al., 2007) , lysine methylation (Ong et al., 2004) or acetylation (Kim et al., 2006) , ubiquitination (Peng et al., 2003) and sumoylation (Andersen et al., 2009; Impens et al., 2014) have been achieved.

T63061

49116-49457

Sentence

denotes

Still successful large-scale measurements of protein phosphorylation (Ficarro et al., 2002; Olsen et al., 2006) , N-glycosylation (Kaji et al., 2007) , lysine methylation (Ong et al., 2004) or acetylation (Kim et al., 2006) , ubiquitination (Peng et al., 2003) and sumoylation (Andersen et al., 2009; Impens et al., 2014) have been achieved.

TextSentencer_T327

49458-49604

Sentence

denotes

To overcome the caveat of low abundance of modified peptides, enrichment methods for instance using anti-phosphotyrosine antibodies are available.

TextSentencer_T327

49458-49604

Sentence

denotes

To overcome the caveat of low abundance of modified peptides, enrichment methods for instance using anti-phosphotyrosine antibodies are available.

T10159

49458-49604

Sentence

denotes

To overcome the caveat of low abundance of modified peptides, enrichment methods for instance using anti-phosphotyrosine antibodies are available.

TextSentencer_T328

49605-49767

Sentence

denotes

Importantly, when measuring PTMs in interaction proteomics samples, which are of much lower complexity than whole cell lysates, PTM identification is facilitated.

TextSentencer_T328

49605-49767

Sentence

denotes

Importantly, when measuring PTMs in interaction proteomics samples, which are of much lower complexity than whole cell lysates, PTM identification is facilitated.

T35705

49605-49767

Sentence

denotes

Importantly, when measuring PTMs in interaction proteomics samples, which are of much lower complexity than whole cell lysates, PTM identification is facilitated.

TextSentencer_T329

49768-49850

Sentence

denotes

For stimuli other than viruses, PTM proteomics has yielded comprehensive datasets.

TextSentencer_T329

49768-49850

Sentence

denotes

For stimuli other than viruses, PTM proteomics has yielded comprehensive datasets.

T22906

49768-49850

Sentence

denotes

For stimuli other than viruses, PTM proteomics has yielded comprehensive datasets.

TextSentencer_T330

49851-50067

Sentence

denotes

For instance, phosphoproteomics of epidermal growth factor (EGF) stimulated HeLa cells unraveled 6600 phosphorylation sites on 2244 proteins, with 14% of the interactions showing an at least 2-fold modulation by EGF.

TextSentencer_T330

49851-50067

Sentence

denotes

For instance, phosphoproteomics of epidermal growth factor (EGF) stimulated HeLa cells unraveled 6600 phosphorylation sites on 2244 proteins, with 14% of the interactions showing an at least 2-fold modulation by EGF.

T68648

49851-50067

Sentence

denotes

For instance, phosphoproteomics of epidermal growth factor (EGF) stimulated HeLa cells unraveled 6600 phosphorylation sites on 2244 proteins, with 14% of the interactions showing an at least 2-fold modulation by EGF.

TextSentencer_T331

50068-50233

Sentence

denotes

The majority of proteins further showed multiple PTM sites with different kinetics highlighting how one protein can integrate numerous signals (Olsen et al., 2006) .

TextSentencer_T331

50068-50233

Sentence

denotes

The majority of proteins further showed multiple PTM sites with different kinetics highlighting how one protein can integrate numerous signals (Olsen et al., 2006) .

T99271

50068-50233

Sentence

denotes

The majority of proteins further showed multiple PTM sites with different kinetics highlighting how one protein can integrate numerous signals (Olsen et al., 2006) .

TextSentencer_T332

50234-50304

Sentence

denotes

This and other studies underline the complexity of receptor signaling.

TextSentencer_T332

50234-50304

Sentence

denotes

This and other studies underline the complexity of receptor signaling.

T85123

50234-50304

Sentence

denotes

This and other studies underline the complexity of receptor signaling.

TextSentencer_T333

50305-50484

Sentence

denotes

How extensively virus-receptor interactions alter the phosphoproteome of a host cell, was demonstrated in a first global description for HIV-1 entry (Wojcechowskyj et al., 2013) .

TextSentencer_T333

50305-50484

Sentence

denotes

How extensively virus-receptor interactions alter the phosphoproteome of a host cell, was demonstrated in a first global description for HIV-1 entry (Wojcechowskyj et al., 2013) .

T95010

50305-50484

Sentence

denotes

How extensively virus-receptor interactions alter the phosphoproteome of a host cell, was demonstrated in a first global description for HIV-1 entry (Wojcechowskyj et al., 2013) .

TextSentencer_T334

50485-50653

Sentence

denotes

A total of 239 phosphorylation sites in 175 proteins changed just one minute after HIV-1 binding and the study disclosed several previously unknown HIV-1 entry factors.

TextSentencer_T334

50485-50653

Sentence

denotes

A total of 239 phosphorylation sites in 175 proteins changed just one minute after HIV-1 binding and the study disclosed several previously unknown HIV-1 entry factors.

T81169

50485-50653

Sentence

denotes

A total of 239 phosphorylation sites in 175 proteins changed just one minute after HIV-1 binding and the study disclosed several previously unknown HIV-1 entry factors.

TextSentencer_T335

50654-50837

Sentence

denotes

It is conceived that most viruses will trigger PTM-dependent signaling during their entry process and this is either critical for cell penetration or for modulating cellular immunity.

TextSentencer_T335

50654-50837

Sentence

denotes

It is conceived that most viruses will trigger PTM-dependent signaling during their entry process and this is either critical for cell penetration or for modulating cellular immunity.

T32513

50654-50837

Sentence

denotes

It is conceived that most viruses will trigger PTM-dependent signaling during their entry process and this is either critical for cell penetration or for modulating cellular immunity.

TextSentencer_T336

50838-51021

Sentence

denotes

Recent developments in PTM proteomics now allow the global mapping of virus induced changes in host proteome PTMs and can thereby disclose signaling pathways active during cell entry.

TextSentencer_T336

50838-51021

Sentence

denotes

Recent developments in PTM proteomics now allow the global mapping of virus induced changes in host proteome PTMs and can thereby disclose signaling pathways active during cell entry.

T83311

50838-51021

Sentence

denotes

Recent developments in PTM proteomics now allow the global mapping of virus induced changes in host proteome PTMs and can thereby disclose signaling pathways active during cell entry.

TextSentencer_T337

51022-51165

Sentence

denotes

The stoichiometric composition of receptor complexes is critical for membrane microdomain localization, signal coordination and ligand binding.

TextSentencer_T337

51022-51165

Sentence

denotes

The stoichiometric composition of receptor complexes is critical for membrane microdomain localization, signal coordination and ligand binding.

T99716

51022-51165

Sentence

denotes

The stoichiometric composition of receptor complexes is critical for membrane microdomain localization, signal coordination and ligand binding.

TextSentencer_T338

51166-51266

Sentence

denotes

Interaction proteomics can provide information on the relative abundances of a protein in a complex.

TextSentencer_T338

51166-51266

Sentence

denotes

Interaction proteomics can provide information on the relative abundances of a protein in a complex.

T25802

51166-51266

Sentence

denotes

Interaction proteomics can provide information on the relative abundances of a protein in a complex.

TextSentencer_T339

51267-51424

Sentence

denotes

Typically prey protein abundance in the pull down is corrected for the prey abundance in a control pull down and subsequently normalized to the bait protein.

TextSentencer_T339

51267-51424

Sentence

denotes

Typically prey protein abundance in the pull down is corrected for the prey abundance in a control pull down and subsequently normalized to the bait protein.

T72949

51267-51424

Sentence

denotes

Typically prey protein abundance in the pull down is corrected for the prey abundance in a control pull down and subsequently normalized to the bait protein.

TextSentencer_T340

51425-51564

Sentence

denotes

This approach was used to estimate the stoichiometry of the YAP and TAZ protein complexes in the human Hippo pathway (Kohli et al., 2014) .

TextSentencer_T340

51425-51564

Sentence

denotes

This approach was used to estimate the stoichiometry of the YAP and TAZ protein complexes in the human Hippo pathway (Kohli et al., 2014) .

T66184

51425-51564

Sentence

denotes

This approach was used to estimate the stoichiometry of the YAP and TAZ protein complexes in the human Hippo pathway (Kohli et al., 2014) .

TextSentencer_T341

51565-51716

Sentence

denotes

Beyond complex stoichiometry measurements, shotgun proteomics now allows to estimate which fraction of a protein is sequestered into a protein complex.

TextSentencer_T341

51565-51716

Sentence

denotes

Beyond complex stoichiometry measurements, shotgun proteomics now allows to estimate which fraction of a protein is sequestered into a protein complex.

T32003

51565-51716

Sentence

denotes

Beyond complex stoichiometry measurements, shotgun proteomics now allows to estimate which fraction of a protein is sequestered into a protein complex.

TextSentencer_T342

51717-51838

Sentence

denotes

Mann and colleagues recently developed a method to estimate protein copy numbers in labelfree proteomes from whole cells.

TextSentencer_T342

51717-51838

Sentence

denotes

Mann and colleagues recently developed a method to estimate protein copy numbers in labelfree proteomes from whole cells.

T86264

51717-51838

Sentence

denotes

Mann and colleagues recently developed a method to estimate protein copy numbers in labelfree proteomes from whole cells.

TextSentencer_T343

51839-52135

Sentence

denotes

This "proteomic ruler" technique determines the absolute abundance of a protein in a cell, based on the fact that the total amount of histones, which is defined by the cell ploidity and genome size, can be used for normalization of any detected protein in a proteomic dataset of sufficient depth.

TextSentencer_T343

51839-52135

Sentence

denotes

This "proteomic ruler" technique determines the absolute abundance of a protein in a cell, based on the fact that the total amount of histones, which is defined by the cell ploidity and genome size, can be used for normalization of any detected protein in a proteomic dataset of sufficient depth.

T7509

51839-52135

Sentence

denotes

This "proteomic ruler" technique determines the absolute abundance of a protein in a cell, based on the fact that the total amount of histones, which is defined by the cell ploidity and genome size, can be used for normalization of any detected protein in a proteomic dataset of sufficient depth.

TextSentencer_T344

52136-52242

Sentence

denotes

The minimum depth of a whole cell proteome to guarantee reliable histone based scaling is 12,000 peptides.

TextSentencer_T344

52136-52242

Sentence

denotes

The minimum depth of a whole cell proteome to guarantee reliable histone based scaling is 12,000 peptides.

T45380

52136-52242

Sentence

denotes

The minimum depth of a whole cell proteome to guarantee reliable histone based scaling is 12,000 peptides.

TextSentencer_T345

52243-52436

Sentence

denotes

This scaling method is similarly accurate as previous spiked-in protein epitope signature tags (PrESTs) based methods, which required cell counting and cell labeling (Wisniewski et al., 2014) .

TextSentencer_T345

52243-52436

Sentence

denotes

This scaling method is similarly accurate as previous spiked-in protein epitope signature tags (PrESTs) based methods, which required cell counting and cell labeling (Wisniewski et al., 2014) .

T86404

52243-52436

Sentence

denotes

This scaling method is similarly accurate as previous spiked-in protein epitope signature tags (PrESTs) based methods, which required cell counting and cell labeling (Wisniewski et al., 2014) .

TextSentencer_T346

52437-52543

Sentence

denotes

Thus, whole cell proteomic datasets can provide information on total protein copy numbers in a given cell.

TextSentencer_T346

52437-52543

Sentence

denotes

Thus, whole cell proteomic datasets can provide information on total protein copy numbers in a given cell.

T2155

52437-52543

Sentence

denotes

Thus, whole cell proteomic datasets can provide information on total protein copy numbers in a given cell.

TextSentencer_T347

52544-52705

Sentence

denotes

Based on this knowledge the receptor complex stoichiometry can be estimated by comparing relative abundances of co-purified proteins in an AE proteomics dataset.

TextSentencer_T347

52544-52705

Sentence

denotes

Based on this knowledge the receptor complex stoichiometry can be estimated by comparing relative abundances of co-purified proteins in an AE proteomics dataset.

T59731

52544-52705

Sentence

denotes

Based on this knowledge the receptor complex stoichiometry can be estimated by comparing relative abundances of co-purified proteins in an AE proteomics dataset.

TextSentencer_T348

52706-52856

Sentence

denotes

Success-ful receptor complex stoichiometry calculation has recently been demonstrated for subcellular fractionation proteomics (Borner et al., 2014) .

TextSentencer_T348

52706-52856

Sentence

denotes

Success-ful receptor complex stoichiometry calculation has recently been demonstrated for subcellular fractionation proteomics (Borner et al., 2014) .

T42547

52706-52856

Sentence

denotes

Success-ful receptor complex stoichiometry calculation has recently been demonstrated for subcellular fractionation proteomics (Borner et al., 2014) .

TextSentencer_T349

52857-53060

Sentence

denotes

Thus, shotgun proteomics goes beyond pure identification of virus entry receptor complexes, but is also suitable to estimate complex stoichiometry and degree of sequestration of a protein into a complex.

TextSentencer_T349

52857-53060

Sentence

denotes

Thus, shotgun proteomics goes beyond pure identification of virus entry receptor complexes, but is also suitable to estimate complex stoichiometry and degree of sequestration of a protein into a complex.

T805

52857-53060

Sentence

denotes

Thus, shotgun proteomics goes beyond pure identification of virus entry receptor complexes, but is also suitable to estimate complex stoichiometry and degree of sequestration of a protein into a complex.

TextSentencer_T350

53061-53251

Sentence

denotes

The era of systems biology and proteomics puts the virologist into the unique position of drawing a comprehensive picture of all molecular interactions during virus infection of a host cell.

TextSentencer_T350

53061-53251

Sentence

denotes

The era of systems biology and proteomics puts the virologist into the unique position of drawing a comprehensive picture of all molecular interactions during virus infection of a host cell.

T32842

53061-53251

Sentence

denotes

The era of systems biology and proteomics puts the virologist into the unique position of drawing a comprehensive picture of all molecular interactions during virus infection of a host cell.

TextSentencer_T351

53252-53479

Sentence

denotes

Large scale genome and transcriptome-based methods for the characterization of virus-host interactions, including mRNA microarrays, RNA interference and cDNA library screens, led to the discovery of a multitude of host factors.

TextSentencer_T351

53252-53479

Sentence

denotes

Large scale genome and transcriptome-based methods for the characterization of virus-host interactions, including mRNA microarrays, RNA interference and cDNA library screens, led to the discovery of a multitude of host factors.

T7457

53252-53479

Sentence

denotes

Large scale genome and transcriptome-based methods for the characterization of virus-host interactions, including mRNA microarrays, RNA interference and cDNA library screens, led to the discovery of a multitude of host factors.

TextSentencer_T352

53480-53642

Sentence

denotes

We currently lack information on the physical interconnection of these host factors and thus it is difficult to identify critical players in virus entry pathways.

TextSentencer_T352

53480-53642

Sentence

denotes

We currently lack information on the physical interconnection of these host factors and thus it is difficult to identify critical players in virus entry pathways.

T47706

53480-53642

Sentence

denotes

We currently lack information on the physical interconnection of these host factors and thus it is difficult to identify critical players in virus entry pathways.

TextSentencer_T353

53643-53939

Sentence

denotes

Open access databases on PPIs like the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) integrate public databases like IntAct and Reactome and can facilitate the mapping of host factors into known networks (Croft et al., 2014; Orchard et al., 2014; Szklarczyk et al., 2015) .

TextSentencer_T353

53643-53939

Sentence

denotes

Open access databases on PPIs like the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) integrate public databases like IntAct and Reactome and can facilitate the mapping of host factors into known networks (Croft et al., 2014; Orchard et al., 2014; Szklarczyk et al., 2015) .

T66441

53643-53939

Sentence

denotes

Open access databases on PPIs like the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) integrate public databases like IntAct and Reactome and can facilitate the mapping of host factors into known networks (Croft et al., 2014; Orchard et al., 2014; Szklarczyk et al., 2015) .

TextSentencer_T354

53940-54017

Sentence

denotes

However, many virus host factors do not map to previously described networks.

TextSentencer_T354

53940-54017

Sentence

denotes

However, many virus host factors do not map to previously described networks.

T72235

53940-54017

Sentence

denotes

However, many virus host factors do not map to previously described networks.

TextSentencer_T355

54018-54102

Sentence

denotes

Also, virus induced changes of cellular PPIs are not deposited in current databases.

TextSentencer_T355

54018-54102

Sentence

denotes

Also, virus induced changes of cellular PPIs are not deposited in current databases.

T54551

54018-54102

Sentence

denotes

Also, virus induced changes of cellular PPIs are not deposited in current databases.

TextSentencer_T356

54103-54261

Sentence

denotes

Some repositories, however, curate host-pathogen interactions, e.g., VirHostNet and the HIVcentric GPSprot site (Fahey et al., 2011; Guirimand et al., 2015) .

TextSentencer_T356

54103-54261

Sentence

denotes

Some repositories, however, curate host-pathogen interactions, e.g., VirHostNet and the HIVcentric GPSprot site (Fahey et al., 2011; Guirimand et al., 2015) .

T89474

54103-54261

Sentence

denotes

Some repositories, however, curate host-pathogen interactions, e.g., VirHostNet and the HIVcentric GPSprot site (Fahey et al., 2011; Guirimand et al., 2015) .

TextSentencer_T357

54262-54393

Sentence

denotes

Importantly, viruses do not play according to the rule, i.e., they may induce PPI that do not normally exist in non-infected cells.

TextSentencer_T357

54262-54393

Sentence

denotes

Importantly, viruses do not play according to the rule, i.e., they may induce PPI that do not normally exist in non-infected cells.

T83646

54262-54393

Sentence

denotes

Importantly, viruses do not play according to the rule, i.e., they may induce PPI that do not normally exist in non-infected cells.

TextSentencer_T358

54394-54550

Sentence

denotes

For instance, they can change the subcellular localization of a host factor and thereby connect pathways, which in an uninfected cell operate independently.

TextSentencer_T358

54394-54550

Sentence

denotes

For instance, they can change the subcellular localization of a host factor and thereby connect pathways, which in an uninfected cell operate independently.

T50679

54394-54550

Sentence

denotes

For instance, they can change the subcellular localization of a host factor and thereby connect pathways, which in an uninfected cell operate independently.

TextSentencer_T359

54551-54749

Sentence

denotes

Thus, existing databases on host PPI may have only limited predictive value for infected cells, in particular at steps of the life cycle that heavily depend on the cell's machinery like virus entry.

TextSentencer_T359

54551-54749

Sentence

denotes

Thus, existing databases on host PPI may have only limited predictive value for infected cells, in particular at steps of the life cycle that heavily depend on the cell's machinery like virus entry.

T39783

54551-54749

Sentence

denotes

Thus, existing databases on host PPI may have only limited predictive value for infected cells, in particular at steps of the life cycle that heavily depend on the cell's machinery like virus entry.

TextSentencer_T360

54750-54847

Sentence

denotes

Again this calls for repositories that either specialize in or integrate PPI from infected cells.

TextSentencer_T360

54750-54847

Sentence

denotes

Again this calls for repositories that either specialize in or integrate PPI from infected cells.

T792

54750-54847

Sentence

denotes

Again this calls for repositories that either specialize in or integrate PPI from infected cells.

TextSentencer_T361

54848-54980

Sentence

denotes

The above described technological advances now enable rapid acquisition of large sets of protein interaction data from one-step AEs.

TextSentencer_T361

54848-54980

Sentence

denotes

The above described technological advances now enable rapid acquisition of large sets of protein interaction data from one-step AEs.

T80119

54848-54980

Sentence

denotes

The above described technological advances now enable rapid acquisition of large sets of protein interaction data from one-step AEs.

TextSentencer_T362

54981-55194

Sentence

denotes

Thus, proteomics is now high throughput compatible and amenable to systems biology studies (Hosp et al., 2015) providing the unprecedented chance to globally define protein-protein networks during virus infection.

TextSentencer_T362

54981-55194

Sentence

denotes

Thus, proteomics is now high throughput compatible and amenable to systems biology studies (Hosp et al., 2015) providing the unprecedented chance to globally define protein-protein networks during virus infection.

T1798

54981-55194

Sentence

denotes

Thus, proteomics is now high throughput compatible and amenable to systems biology studies (Hosp et al., 2015) providing the unprecedented chance to globally define protein-protein networks during virus infection.

TextSentencer_T363

55195-55415

Sentence

denotes

Critical for high confidence network generation and data deposition is the analysis of a large number of biological replicates, experimental conditions and controls including immunoprecipitates from bait deficient cells.

TextSentencer_T363

55195-55415

Sentence

denotes

Critical for high confidence network generation and data deposition is the analysis of a large number of biological replicates, experimental conditions and controls including immunoprecipitates from bait deficient cells.

T48406

55195-55415

Sentence

denotes

Critical for high confidence network generation and data deposition is the analysis of a large number of biological replicates, experimental conditions and controls including immunoprecipitates from bait deficient cells.

TextSentencer_T364

55416-55606

Sentence

denotes

Furthermore, several laboratories performed control pull-downs under various experimental conditions and established a "contaminant repository for AP" (CRAPome) (Mellacheruvu et al., 2013) .

TextSentencer_T364

55416-55606

Sentence

denotes

Furthermore, several laboratories performed control pull-downs under various experimental conditions and established a "contaminant repository for AP" (CRAPome) (Mellacheruvu et al., 2013) .

T24645

55416-55606

Sentence

denotes

Furthermore, several laboratories performed control pull-downs under various experimental conditions and established a "contaminant repository for AP" (CRAPome) (Mellacheruvu et al., 2013) .

TextSentencer_T365

55607-55770

Sentence

denotes

However, background binders can critically differ between experimental setups and thus a universal CRAPome is problematic, making internal controls more reliable .

TextSentencer_T365

55607-55770

Sentence

denotes

However, background binders can critically differ between experimental setups and thus a universal CRAPome is problematic, making internal controls more reliable .

T71533

55607-55770

Sentence

denotes

However, background binders can critically differ between experimental setups and thus a universal CRAPome is problematic, making internal controls more reliable .

TextSentencer_T366

55771-55904

Sentence

denotes

Clearly, newly acquired datasets on virus infection interactomes should be integrated into established host protein-protein networks.

TextSentencer_T366

55771-55904

Sentence

denotes

Clearly, newly acquired datasets on virus infection interactomes should be integrated into established host protein-protein networks.

T14309

55771-55904

Sentence

denotes

Clearly, newly acquired datasets on virus infection interactomes should be integrated into established host protein-protein networks.

TextSentencer_T367

55905-56099

Sentence

denotes

Currently, the above mentioned VirHostNet is probably the most comprehensive database for virus-host interactions, which directly links interaction partners to UniProt (Guirimand et al., 2015) .

TextSentencer_T367

55905-56099

Sentence

denotes

Currently, the above mentioned VirHostNet is probably the most comprehensive database for virus-host interactions, which directly links interaction partners to UniProt (Guirimand et al., 2015) .

T85977

55905-56099

Sentence

denotes

Currently, the above mentioned VirHostNet is probably the most comprehensive database for virus-host interactions, which directly links interaction partners to UniProt (Guirimand et al., 2015) .

TextSentencer_T368

56100-56374

Sentence

denotes

As many pathogens share mechanisms for exploiting host cells, a central database for host-pathogen interactions, multiplexing datasets for viruses, bacteria, fungi and parasites would allow the rapid identification of critical nodes and putative broad spectrum drug targets.

TextSentencer_T368

56100-56374

Sentence

denotes

As many pathogens share mechanisms for exploiting host cells, a central database for host-pathogen interactions, multiplexing datasets for viruses, bacteria, fungi and parasites would allow the rapid identification of critical nodes and putative broad spectrum drug targets.

T59044

56100-56374

Sentence

denotes

As many pathogens share mechanisms for exploiting host cells, a central database for host-pathogen interactions, multiplexing datasets for viruses, bacteria, fungi and parasites would allow the rapid identification of critical nodes and putative broad spectrum drug targets.

TextSentencer_T369

56375-56563

Sentence

denotes

Clearly, publically available databases should reliably catalogue virus-host interactions and make these easily accessible to the virologist community through user-friendly web interfaces.

TextSentencer_T369

56375-56563

Sentence

denotes

Clearly, publically available databases should reliably catalogue virus-host interactions and make these easily accessible to the virologist community through user-friendly web interfaces.

T61093

56375-56563

Sentence

denotes

Clearly, publically available databases should reliably catalogue virus-host interactions and make these easily accessible to the virologist community through user-friendly web interfaces.

TextSentencer_T370

56564-56695

Sentence

denotes

Ultimately, genomics and proteomics techniques provide essential complementary datasets, which can be integrated to reveal a Box 3:

TextSentencer_T370

56564-56695

Sentence

denotes

Ultimately, genomics and proteomics techniques provide essential complementary datasets, which can be integrated to reveal a Box 3:

T93782

56564-56695

Sentence

denotes

Ultimately, genomics and proteomics techniques provide essential complementary datasets, which can be integrated to reveal a Box 3:

TextSentencer_T371

56696-56721

Sentence

denotes

Network term definitions.

TextSentencer_T371

56696-56721

Sentence

denotes

Network term definitions.

T69515

56696-56721

Sentence

denotes

Network term definitions.

TextSentencer_T372

56722-56778

Sentence

denotes

Node: component of a network, e.g., a gene or a protein.

TextSentencer_T372

56722-56778

Sentence

denotes

Node: component of a network, e.g., a gene or a protein.

T3264

56722-56778

Sentence

denotes

Node: component of a network, e.g., a gene or a protein.

TextSentencer_T373

56779-56874

Sentence

denotes

Hub: node, which is highly connected and therefore a point of control of a specific subnetwork.

TextSentencer_T373

56779-56874

Sentence

denotes

Hub: node, which is highly connected and therefore a point of control of a specific subnetwork.

T99629

56779-56874

Sentence

denotes

Hub: node, which is highly connected and therefore a point of control of a specific subnetwork.

TextSentencer_T374

56875-56967

Sentence

denotes

Bottleneck: node, which connects subnetworks and thus critically restricts information flow.

TextSentencer_T374

56875-56967

Sentence

denotes

Bottleneck: node, which connects subnetworks and thus critically restricts information flow.

T26426

56875-56967

Sentence

denotes

Bottleneck: node, which connects subnetworks and thus critically restricts information flow.

TextSentencer_T375

56968-57070

Sentence

denotes

Edge: connection of two nodes in a network, e.g., representing a physical interaction of two proteins.

TextSentencer_T375

56968-57070

Sentence

denotes

Edge: connection of two nodes in a network, e.g., representing a physical interaction of two proteins.

T34191

56968-57070

Sentence

denotes

Edge: connection of two nodes in a network, e.g., representing a physical interaction of two proteins.

TextSentencer_T376

57071-57136

Sentence

denotes

most complete picture of molecular events during virus infection.

TextSentencer_T376

57071-57136

Sentence

denotes

most complete picture of molecular events during virus infection.

T12181

57071-57136

Sentence

denotes

most complete picture of molecular events during virus infection.

TextSentencer_T377

57137-57263

Sentence

denotes

Functional genomics screens can weigh the importance of a host factor in an interaction network and reveal redundant pathways.

TextSentencer_T377

57137-57263

Sentence

denotes

Functional genomics screens can weigh the importance of a host factor in an interaction network and reveal redundant pathways.

T41787

57137-57263

Sentence

denotes

Functional genomics screens can weigh the importance of a host factor in an interaction network and reveal redundant pathways.

TextSentencer_T378

57264-57384

Sentence

denotes

Annotation clusters can highlight the enrichment of certain cellular processes, molecular functions or protein domains .

TextSentencer_T378

57264-57384

Sentence

denotes

Annotation clusters can highlight the enrichment of certain cellular processes, molecular functions or protein domains .

T93746

57264-57384

Sentence

denotes

Annotation clusters can highlight the enrichment of certain cellular processes, molecular functions or protein domains .

TextSentencer_T379

57385-57522

Sentence

denotes

Novel open access bioinformatics solutions building on available resources like STRING and DAVID can help harmonizing available datasets.

TextSentencer_T379

57385-57522

Sentence

denotes

Novel open access bioinformatics solutions building on available resources like STRING and DAVID can help harmonizing available datasets.

T27282

57385-57522

Sentence

denotes

Novel open access bioinformatics solutions building on available resources like STRING and DAVID can help harmonizing available datasets.

TextSentencer_T380

57523-57786

Sentence

denotes

Scripting and visualization environments like Cytoscape, R and Bioconductor, which were previously developed for transcriptomics and genomics data integration, are also suitable for pathway mapping of proteomics data (Cline et al., 2007; Gentleman et al., 2004) .

TextSentencer_T380

57523-57786

Sentence

denotes

Scripting and visualization environments like Cytoscape, R and Bioconductor, which were previously developed for transcriptomics and genomics data integration, are also suitable for pathway mapping of proteomics data (Cline et al., 2007; Gentleman et al., 2004) .

T61527

57523-57786

Sentence

denotes

Scripting and visualization environments like Cytoscape, R and Bioconductor, which were previously developed for transcriptomics and genomics data integration, are also suitable for pathway mapping of proteomics data (Cline et al., 2007; Gentleman et al., 2004) .

TextSentencer_T381

57787-57937

Sentence

denotes

Proteomics-specific and publically available programs like Perseus provide an additional tool for data analysis and integration (Cox and Mann, 2012) .

TextSentencer_T381

57787-57937

Sentence

denotes

Proteomics-specific and publically available programs like Perseus provide an additional tool for data analysis and integration (Cox and Mann, 2012) .

T21484

57787-57937

Sentence

denotes

Proteomics-specific and publically available programs like Perseus provide an additional tool for data analysis and integration (Cox and Mann, 2012) .

TextSentencer_T382

57938-58134

Sentence

denotes

Meta-analysis of omics datasets together with sharing of data in a timely manner will be critical to successfully model the complexity of virus-host interactions in the future (Law et al., 2013) .

TextSentencer_T382

57938-58134

Sentence

denotes

Meta-analysis of omics datasets together with sharing of data in a timely manner will be critical to successfully model the complexity of virus-host interactions in the future (Law et al., 2013) .

T84018

57938-58134

Sentence

denotes

Meta-analysis of omics datasets together with sharing of data in a timely manner will be critical to successfully model the complexity of virus-host interactions in the future (Law et al., 2013) .

TextSentencer_T383

58135-58263

Sentence

denotes

Such networks will then allow the identification of essential nodes, bottlenecks and hubs for selection of optimal drug targets.

TextSentencer_T383

58135-58263

Sentence

denotes

Such networks will then allow the identification of essential nodes, bottlenecks and hubs for selection of optimal drug targets.

T56427

58135-58263

Sentence

denotes

Such networks will then allow the identification of essential nodes, bottlenecks and hubs for selection of optimal drug targets.

TextSentencer_T384

58264-58351

Sentence

denotes

Each node in a PPI network represents a protein, while the edges indicate interactions.

TextSentencer_T384

58264-58351

Sentence

denotes

Each node in a PPI network represents a protein, while the edges indicate interactions.

T14101

58264-58351

Sentence

denotes

Each node in a PPI network represents a protein, while the edges indicate interactions.

TextSentencer_T385

58352-58510

Sentence

denotes

Bottlenecks are nodes in a network, which critically connect subnetworks and thus restrict information flow, like e.g. central kinases in a signaling pathway.

TextSentencer_T385

58352-58510

Sentence

denotes

Bottlenecks are nodes in a network, which critically connect subnetworks and thus restrict information flow, like e.g. central kinases in a signaling pathway.

T22744

58352-58510

Sentence

denotes

Bottlenecks are nodes in a network, which critically connect subnetworks and thus restrict information flow, like e.g. central kinases in a signaling pathway.

TextSentencer_T386

58511-58649

Sentence

denotes

Hubs instead are highly interlinked and therefore central points of control, but typically only control one branch of a signaling pathway.

TextSentencer_T386

58511-58649

Sentence

denotes

Hubs instead are highly interlinked and therefore central points of control, but typically only control one branch of a signaling pathway.

T63961

58511-58649

Sentence

denotes

Hubs instead are highly interlinked and therefore central points of control, but typically only control one branch of a signaling pathway.

TextSentencer_T387

58650-58834

Sentence

denotes

While bottlenecks are less attractive drug targets as their inhibition would shut down complete endogenous pathways, hub inhibition can lead to an efficient block of infection (Box 3).

TextSentencer_T387

58650-58834

Sentence

denotes

While bottlenecks are less attractive drug targets as their inhibition would shut down complete endogenous pathways, hub inhibition can lead to an efficient block of infection (Box 3).

T96580

58650-58834

Sentence

denotes

While bottlenecks are less attractive drug targets as their inhibition would shut down complete endogenous pathways, hub inhibition can lead to an efficient block of infection (Box 3).

TextSentencer_T388

58835-59030

Sentence

denotes

Furthermore, drug targeting of pathogen relevant PPIs using small molecule drugs or peptidomimetics seems an attractive strategy to combat infection (de Chassey et al., 2012a; Law et al., 2013) .

TextSentencer_T388

58835-59030

Sentence

denotes

Furthermore, drug targeting of pathogen relevant PPIs using small molecule drugs or peptidomimetics seems an attractive strategy to combat infection (de Chassey et al., 2012a; Law et al., 2013) .

T60254

58835-59030

Sentence

denotes

Furthermore, drug targeting of pathogen relevant PPIs using small molecule drugs or peptidomimetics seems an attractive strategy to combat infection (de Chassey et al., 2012a; Law et al., 2013) .

TextSentencer_T389

59031-59145

Sentence

denotes

In particular, targeting of interfaces between viral and host proteins, holds the promise of minimal side effects.

TextSentencer_T389

59031-59145

Sentence

denotes

In particular, targeting of interfaces between viral and host proteins, holds the promise of minimal side effects.

T51581

59031-59145

Sentence

denotes

In particular, targeting of interfaces between viral and host proteins, holds the promise of minimal side effects.

TextSentencer_T390

59146-59252

Sentence

denotes

But even host PPIs, which are triggered or exploited during virus infection, represent attractive targets.

TextSentencer_T390

59146-59252

Sentence

denotes

But even host PPIs, which are triggered or exploited during virus infection, represent attractive targets.

T48254

59146-59252

Sentence

denotes

But even host PPIs, which are triggered or exploited during virus infection, represent attractive targets.

TextSentencer_T391

59253-59496

Sentence

denotes

In contrast to direct acting antivirals, which often lead to rapid emergence of viral resistance mutations, host proteins and thus their interactions represent a high evolutionary barrier (Gerold and Pietschmann, 2014; von Hahn et al., 2011) .

TextSentencer_T391

59253-59496

Sentence

denotes

In contrast to direct acting antivirals, which often lead to rapid emergence of viral resistance mutations, host proteins and thus their interactions represent a high evolutionary barrier (Gerold and Pietschmann, 2014; von Hahn et al., 2011) .

T167

59253-59496

Sentence

denotes

In contrast to direct acting antivirals, which often lead to rapid emergence of viral resistance mutations, host proteins and thus their interactions represent a high evolutionary barrier (Gerold and Pietschmann, 2014; von Hahn et al., 2011) .

TextSentencer_T392

59497-59678

Sentence

denotes

In particular, host proteases and kinases are attractive drug targets and both protein classes can be identified by advanced interaction proteomics and PTM proteomics, respectively.

TextSentencer_T392

59497-59678

Sentence

denotes

In particular, host proteases and kinases are attractive drug targets and both protein classes can be identified by advanced interaction proteomics and PTM proteomics, respectively.

T5800

59497-59678

Sentence

denotes

In particular, host proteases and kinases are attractive drug targets and both protein classes can be identified by advanced interaction proteomics and PTM proteomics, respectively.

TextSentencer_T393

59679-59856

Sentence

denotes

Taken together, increasing knowledge on interactomes during virus infection and the compilation of interactome datasets can spur the development of novel antiviral therapeutics.

TextSentencer_T393

59679-59856

Sentence

denotes

Taken together, increasing knowledge on interactomes during virus infection and the compilation of interactome datasets can spur the development of novel antiviral therapeutics.

T76367

59679-59856

Sentence

denotes

Taken together, increasing knowledge on interactomes during virus infection and the compilation of interactome datasets can spur the development of novel antiviral therapeutics.

TextSentencer_T394

59857-59961

Sentence

denotes

The experimental validation of central network hubs, also as potential drug targets, is discussed below.

TextSentencer_T394

59857-59961

Sentence

denotes

The experimental validation of central network hubs, also as potential drug targets, is discussed below.

T81162

59857-59961

Sentence

denotes

The experimental validation of central network hubs, also as potential drug targets, is discussed below.

TextSentencer_T395

59962-60154

Sentence

denotes

Protein interaction network analysis allows in the next step to hypothesize, which biological pathway is critical for virus uptake and whether certain proteins are central hubs in the network.

TextSentencer_T395

59962-60154

Sentence

denotes

Protein interaction network analysis allows in the next step to hypothesize, which biological pathway is critical for virus uptake and whether certain proteins are central hubs in the network.

T57865

59962-60154

Sentence

denotes

Protein interaction network analysis allows in the next step to hypothesize, which biological pathway is critical for virus uptake and whether certain proteins are central hubs in the network.

TextSentencer_T396

60155-60299

Sentence

denotes

The hypothesis can then be tested by disrupting the function of one of the interaction partners and studying the resulting phenotype (Fig. 3D) .

TextSentencer_T396

60155-60299

Sentence

denotes

The hypothesis can then be tested by disrupting the function of one of the interaction partners and studying the resulting phenotype (Fig. 3D) .

T950

60155-60299

Sentence

denotes

The hypothesis can then be tested by disrupting the function of one of the interaction partners and studying the resulting phenotype (Fig. 3D) .

TextSentencer_T397

60300-60425

Sentence

denotes

To this end, blocking antibodies have been used, but the method is limited to proteins with accessible extracellular domains.

TextSentencer_T397

60300-60425

Sentence

denotes

To this end, blocking antibodies have been used, but the method is limited to proteins with accessible extracellular domains.

T71892

60300-60425

Sentence

denotes

To this end, blocking antibodies have been used, but the method is limited to proteins with accessible extracellular domains.

TextSentencer_T398

60426-60516

Sentence

denotes

Alternatively, small molecule inhibitors, if available, can block the protein of interest.

TextSentencer_T398

60426-60516

Sentence

denotes

Alternatively, small molecule inhibitors, if available, can block the protein of interest.

T1012

60426-60516

Sentence

denotes

Alternatively, small molecule inhibitors, if available, can block the protein of interest.

TextSentencer_T399

60517-60688

Sentence

denotes

Due to their microreversibility and rapid mode of action, such molecular probes have in the past proven indispensable to dissect the kinetics of virus-host cell interplay.

TextSentencer_T399

60517-60688

Sentence

denotes

Due to their microreversibility and rapid mode of action, such molecular probes have in the past proven indispensable to dissect the kinetics of virus-host cell interplay.

T32482

60517-60688

Sentence

denotes

Due to their microreversibility and rapid mode of action, such molecular probes have in the past proven indispensable to dissect the kinetics of virus-host cell interplay.

TextSentencer_T400

60689-60886

Sentence

denotes

The most commonly used strategy to address a protein's function was in the past the disruption or reduction of its expression by RNA interference (RNAi) (Elbashir et al., 2001; Fire et al., 1998) .

TextSentencer_T400

60689-60886

Sentence

denotes

The most commonly used strategy to address a protein's function was in the past the disruption or reduction of its expression by RNA interference (RNAi) (Elbashir et al., 2001; Fire et al., 1998) .

T96846

60689-60886

Sentence

denotes

The most commonly used strategy to address a protein's function was in the past the disruption or reduction of its expression by RNA interference (RNAi) (Elbashir et al., 2001; Fire et al., 1998) .

TextSentencer_T401

60887-60991

Sentence

denotes

Here, short RNA molecules sequence-specifically target complementary mRNAs and induce their degradation.

TextSentencer_T401

60887-60991

Sentence

denotes

Here, short RNA molecules sequence-specifically target complementary mRNAs and induce their degradation.

T54874

60887-60991

Sentence

denotes

Here, short RNA molecules sequence-specifically target complementary mRNAs and induce their degradation.

TextSentencer_T402

60992-61108

Sentence

denotes

RNAi has been used to address the role of protein interactions identified by MS in virus entry (Zona et al., 2013) .

TextSentencer_T402

60992-61108

Sentence

denotes

RNAi has been used to address the role of protein interactions identified by MS in virus entry (Zona et al., 2013) .

T34138

60992-61108

Sentence

denotes

RNAi has been used to address the role of protein interactions identified by MS in virus entry (Zona et al., 2013) .

TextSentencer_T403

61109-61300

Sentence

denotes

However, RNAi approaches can have offtarget effects (reviewed e.g., in (Mohr et al., 2014) ) and the slow kinetics of action of two to three days can lead to compensatory adaptation of cells.

TextSentencer_T403

61109-61300

Sentence

denotes

However, RNAi approaches can have offtarget effects (reviewed e.g., in (Mohr et al., 2014) ) and the slow kinetics of action of two to three days can lead to compensatory adaptation of cells.

T2220

61109-61300

Sentence

denotes

However, RNAi approaches can have offtarget effects (reviewed e.g., in (Mohr et al., 2014) ) and the slow kinetics of action of two to three days can lead to compensatory adaptation of cells.

TextSentencer_T404

61301-61464

Sentence

denotes

This might be the reason why large-scale RNAi screens performed poorly in studies of virus entry, which operates at a minute timescale (de Chassey et al., 2012b) .

TextSentencer_T404

61301-61464

Sentence

denotes

This might be the reason why large-scale RNAi screens performed poorly in studies of virus entry, which operates at a minute timescale (de Chassey et al., 2012b) .

T87947

61301-61464

Sentence

denotes

This might be the reason why large-scale RNAi screens performed poorly in studies of virus entry, which operates at a minute timescale (de Chassey et al., 2012b) .

TextSentencer_T405

61465-61579

Sentence

denotes

Since 2012, targeted genome editing became possible making use of a bacterial adaptive antiviral immune mechanism.

TextSentencer_T405

61465-61579

Sentence

denotes

Since 2012, targeted genome editing became possible making use of a bacterial adaptive antiviral immune mechanism.

T12218

61465-61579

Sentence

denotes

Since 2012, targeted genome editing became possible making use of a bacterial adaptive antiviral immune mechanism.

TextSentencer_T406

61580-61831

Sentence

denotes

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with the RNA guided DNA endonuclease CRISPR associated protein 9 (Cas9) is able to induce specific DNA double strand breaks (Gasiunas et al., 2012; Jinek et al., 2012) .

TextSentencer_T406

61580-61831

Sentence

denotes

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with the RNA guided DNA endonuclease CRISPR associated protein 9 (Cas9) is able to induce specific DNA double strand breaks (Gasiunas et al., 2012; Jinek et al., 2012) .

T37216

61580-61831

Sentence

denotes

Clustered regularly interspaced short palindromic repeats (CRISPR) in combination with the RNA guided DNA endonuclease CRISPR associated protein 9 (Cas9) is able to induce specific DNA double strand breaks (Gasiunas et al., 2012; Jinek et al., 2012) .

TextSentencer_T407

61832-62005

Sentence

denotes

Therefore, the system can be used to generate site-specific modifications in genomes, e.g. to knock-out specific proteins (reviewed e.g. in (Doudna and Charpentier, 2014) ).

TextSentencer_T407

61832-62005

Sentence

denotes

Therefore, the system can be used to generate site-specific modifications in genomes, e.g. to knock-out specific proteins (reviewed e.g. in (Doudna and Charpentier, 2014) ).

T57498

61832-62005

Sentence

denotes

Therefore, the system can be used to generate site-specific modifications in genomes, e.g. to knock-out specific proteins (reviewed e.g. in (Doudna and Charpentier, 2014) ).

TextSentencer_T408

62006-62131

Sentence

denotes

The CRISPR-Cas9 technology has already been applied to analyze the function of different proteins in the viral entry process.

TextSentencer_T408

62006-62131

Sentence

denotes

The CRISPR-Cas9 technology has already been applied to analyze the function of different proteins in the viral entry process.

T55460

62006-62131

Sentence

denotes

The CRISPR-Cas9 technology has already been applied to analyze the function of different proteins in the viral entry process.

TextSentencer_T409

62132-62267

Sentence

denotes

For example CRISPR-Cas9 knock-out of PDZD8 verified its role in HIV-1 and murine leukemia virus infections (Zhang and Sodroski, 2015) .

TextSentencer_T409

62132-62267

Sentence

denotes

For example CRISPR-Cas9 knock-out of PDZD8 verified its role in HIV-1 and murine leukemia virus infections (Zhang and Sodroski, 2015) .

T83109

62132-62267

Sentence

denotes

For example CRISPR-Cas9 knock-out of PDZD8 verified its role in HIV-1 and murine leukemia virus infections (Zhang and Sodroski, 2015) .

TextSentencer_T410

62268-62460

Sentence

denotes

In a different approach, a genome wide lentiviral CRISPR-Cas9 library was developed to screen for cellular factors essential for entry and cell-to-cell transmission of HCV (Ren et al., 2015) .

TextSentencer_T410

62268-62460

Sentence

denotes

In a different approach, a genome wide lentiviral CRISPR-Cas9 library was developed to screen for cellular factors essential for entry and cell-to-cell transmission of HCV (Ren et al., 2015) .

T82732

62268-62460

Sentence

denotes

In a different approach, a genome wide lentiviral CRISPR-Cas9 library was developed to screen for cellular factors essential for entry and cell-to-cell transmission of HCV (Ren et al., 2015) .

TextSentencer_T411

62461-62550

Sentence

denotes

In this screen, the known HCV entry factors CD81, claudin-1 and occludin were identified.

TextSentencer_T411

62461-62550

Sentence

denotes

In this screen, the known HCV entry factors CD81, claudin-1 and occludin were identified.

T25561

62461-62550

Sentence

denotes

In this screen, the known HCV entry factors CD81, claudin-1 and occludin were identified.

TextSentencer_T412

62551-62808

Sentence

denotes

While knock-out strategies are limited to host factors with non-essential endogenous function and similar to RNAi compensatory effects can occur, a genetically clean knock-out system holds the promise of unambiguously defining essential virus entry factors.

TextSentencer_T412

62551-62808

Sentence

denotes

While knock-out strategies are limited to host factors with non-essential endogenous function and similar to RNAi compensatory effects can occur, a genetically clean knock-out system holds the promise of unambiguously defining essential virus entry factors.

T82218

62551-62808

Sentence

denotes

While knock-out strategies are limited to host factors with non-essential endogenous function and similar to RNAi compensatory effects can occur, a genetically clean knock-out system holds the promise of unambiguously defining essential virus entry factors.

TextSentencer_T413

62809-62947

Sentence

denotes

Future studies will show whether knockout screens have higher reproducibility than RNAi screens and are suitable for virus entry research.

TextSentencer_T413

62809-62947

Sentence

denotes

Future studies will show whether knockout screens have higher reproducibility than RNAi screens and are suitable for virus entry research.

T67575

62809-62947

Sentence

denotes

Future studies will show whether knockout screens have higher reproducibility than RNAi screens and are suitable for virus entry research.

TextSentencer_T414

62948-63080

Sentence

denotes

Both techniques, RNAi and CRISPR-Cas9, display specific advantages and disadvantages, as reviewed in (Boettcher and McManus, 2015) .

TextSentencer_T414

62948-63080

Sentence

denotes

Both techniques, RNAi and CRISPR-Cas9, display specific advantages and disadvantages, as reviewed in (Boettcher and McManus, 2015) .

T414

62948-63080

Sentence

denotes

Both techniques, RNAi and CRISPR-Cas9, display specific advantages and disadvantages, as reviewed in (Boettcher and McManus, 2015) .

TextSentencer_T415

63081-63292

Sentence

denotes

Therefore, the appropriate technique, including small molecule inhibitors, dominant negative variants and blocking antibodies, has to be chosen carefully depending on the experimental setup and the target genes.

TextSentencer_T415

63081-63292

Sentence

denotes

Therefore, the appropriate technique, including small molecule inhibitors, dominant negative variants and blocking antibodies, has to be chosen carefully depending on the experimental setup and the target genes.

T19564

63081-63292

Sentence

denotes

Therefore, the appropriate technique, including small molecule inhibitors, dominant negative variants and blocking antibodies, has to be chosen carefully depending on the experimental setup and the target genes.

TextSentencer_T416

63293-63424

Sentence

denotes

After hypothesis testing, drug targets can be defined and searches for compounds interfering with critical network nodes initiated.

TextSentencer_T416

63293-63424

Sentence

denotes

After hypothesis testing, drug targets can be defined and searches for compounds interfering with critical network nodes initiated.

T99639

63293-63424

Sentence

denotes

After hypothesis testing, drug targets can be defined and searches for compounds interfering with critical network nodes initiated.

TextSentencer_T417

63425-63547

Sentence

denotes

Alternatively, novel baits can be selected and fueled into a new round of AE-MS, thereby widening the interaction network.

TextSentencer_T417

63425-63547

Sentence

denotes

Alternatively, novel baits can be selected and fueled into a new round of AE-MS, thereby widening the interaction network.

T36282

63425-63547

Sentence

denotes

Alternatively, novel baits can be selected and fueled into a new round of AE-MS, thereby widening the interaction network.

TextSentencer_T418

63548-63649

Sentence

denotes

Such iterative processes will ultimately complete the picture of PPI during virus invasion (Fig. 4) .

TextSentencer_T418

63548-63649

Sentence

denotes

Such iterative processes will ultimately complete the picture of PPI during virus invasion (Fig. 4) .

T56702

63548-63649

Sentence

denotes

Such iterative processes will ultimately complete the picture of PPI during virus invasion (Fig. 4) .

TextSentencer_T419

63650-63779

Sentence

denotes

Proteomics is the only method to directly characterize the biologically active entity of most biological processes, the proteins.

TextSentencer_T419

63650-63779

Sentence

denotes

Proteomics is the only method to directly characterize the biologically active entity of most biological processes, the proteins.

T82597

63650-63779

Sentence

denotes

Proteomics is the only method to directly characterize the biologically active entity of most biological processes, the proteins.

TextSentencer_T420

63780-63923

Sentence

denotes

In an AE setup, it provides information on primary protein interactions and higher order complexes depending on the stringency of purification.

TextSentencer_T420

63780-63923

Sentence

denotes

In an AE setup, it provides information on primary protein interactions and higher order complexes depending on the stringency of purification.

T66464

63780-63923

Sentence

denotes

In an AE setup, it provides information on primary protein interactions and higher order complexes depending on the stringency of purification.

TextSentencer_T421

63924-64071

Sentence

denotes

It can further yield the order of binding as well as interaction interfaces, when crosslinkers are used (Chen et al., 2010; Leitner et al., 2010) .

TextSentencer_T421

63924-64071

Sentence

denotes

It can further yield the order of binding as well as interaction interfaces, when crosslinkers are used (Chen et al., 2010; Leitner et al., 2010) .

T87450

63924-64071

Sentence

denotes

It can further yield the order of binding as well as interaction interfaces, when crosslinkers are used (Chen et al., 2010; Leitner et al., 2010) .

TextSentencer_T422

64072-64196

Sentence

denotes

As detailed above, interaction proteomics can reveal receptor complex stoichiometry as well as PTM of the analyzed proteins.

TextSentencer_T422

64072-64196

Sentence

denotes

As detailed above, interaction proteomics can reveal receptor complex stoichiometry as well as PTM of the analyzed proteins.

T80273

64072-64196

Sentence

denotes

As detailed above, interaction proteomics can reveal receptor complex stoichiometry as well as PTM of the analyzed proteins.

TextSentencer_T423

64197-64339

Sentence

denotes

With increasing instrument sensitivity not only stable protein interactions, but also transient and virus-induced interactions are accessible.

TextSentencer_T423

64197-64339

Sentence

denotes

With increasing instrument sensitivity not only stable protein interactions, but also transient and virus-induced interactions are accessible.

T57167

64197-64339

Sentence

denotes

With increasing instrument sensitivity not only stable protein interactions, but also transient and virus-induced interactions are accessible.

TextSentencer_T424

64340-64472

Sentence

denotes

Protein networks between two cellular states, e.g., with and without receptor bound virus, can be compared in a quantitative manner.

TextSentencer_T424

64340-64472

Sentence

denotes

Protein networks between two cellular states, e.g., with and without receptor bound virus, can be compared in a quantitative manner.

T74775

64340-64472

Sentence

denotes

Protein networks between two cellular states, e.g., with and without receptor bound virus, can be compared in a quantitative manner.

TextSentencer_T425

64473-64641

Sentence

denotes

In the past, detection of subtle differences in protein abundance required isotope labeling, but label-free methods are nowadays sensitive enough for most applications.

TextSentencer_T425

64473-64641

Sentence

denotes

In the past, detection of subtle differences in protein abundance required isotope labeling, but label-free methods are nowadays sensitive enough for most applications.

T31076

64473-64641

Sentence

denotes

In the past, detection of subtle differences in protein abundance required isotope labeling, but label-free methods are nowadays sensitive enough for most applications.

TextSentencer_T426

64642-64839

Sentence

denotes

A clear advantage over RNA interference or image-based screens is that the host cell is in its endogenous state without the requirement for labeling of proteins or change of their expression level.

TextSentencer_T426

64642-64839

Sentence

denotes

A clear advantage over RNA interference or image-based screens is that the host cell is in its endogenous state without the requirement for labeling of proteins or change of their expression level.

T16625

64642-64839

Sentence

denotes

A clear advantage over RNA interference or image-based screens is that the host cell is in its endogenous state without the requirement for labeling of proteins or change of their expression level.

TextSentencer_T427

64840-65056

Sentence

denotes

Recent developments moreover make proteomics high throughput screen compatible (Hosp et al., 2015) , so that virus entry processes could be studied in a large panel of cell lines as well as in a time resolved manner.

TextSentencer_T427

64840-65056

Sentence

denotes

Recent developments moreover make proteomics high throughput screen compatible (Hosp et al., 2015) , so that virus entry processes could be studied in a large panel of cell lines as well as in a time resolved manner.

T91478

64840-65056

Sentence

denotes

Recent developments moreover make proteomics high throughput screen compatible (Hosp et al., 2015) , so that virus entry processes could be studied in a large panel of cell lines as well as in a time resolved manner.

TextSentencer_T428

65057-65110

Sentence

denotes

As every method, proteomics has its own shortcomings.

TextSentencer_T428

65057-65110

Sentence

denotes

As every method, proteomics has its own shortcomings.

T95784

65057-65110

Sentence

denotes

As every method, proteomics has its own shortcomings.

TextSentencer_T429

65111-65277

Sentence

denotes

Certain proteins are detected as common contaminants and these false positives have to be eliminated using proper controls and by comparison to contaminant databases.

TextSentencer_T429

65111-65277

Sentence

denotes

Certain proteins are detected as common contaminants and these false positives have to be eliminated using proper controls and by comparison to contaminant databases.

T6818

65111-65277

Sentence

denotes

Certain proteins are detected as common contaminants and these false positives have to be eliminated using proper controls and by comparison to contaminant databases.

TextSentencer_T430

65278-65378

Sentence

denotes

When searching for interactions of endogenous proteins, antibodies of high specificity are required.

TextSentencer_T430

65278-65378

Sentence

denotes

When searching for interactions of endogenous proteins, antibodies of high specificity are required.

T9988

65278-65378

Sentence

denotes

When searching for interactions of endogenous proteins, antibodies of high specificity are required.

TextSentencer_T431

65379-65518

Sentence

denotes

In the future, CRISPR knockin methods might overcome this caveat and allow expression of affinity tagged proteins from their natural locus.

TextSentencer_T431

65379-65518

Sentence

denotes

In the future, CRISPR knockin methods might overcome this caveat and allow expression of affinity tagged proteins from their natural locus.

T33668

65379-65518

Sentence

denotes

In the future, CRISPR knockin methods might overcome this caveat and allow expression of affinity tagged proteins from their natural locus.

TextSentencer_T432

65519-65663

Sentence

denotes

Alternatively, controlled expression systems, although not under endogenous gene control, can help express tagged proteins at endogenous levels.

TextSentencer_T432

65519-65663

Sentence

denotes

Alternatively, controlled expression systems, although not under endogenous gene control, can help express tagged proteins at endogenous levels.

T95148

65519-65663

Sentence

denotes

Alternatively, controlled expression systems, although not under endogenous gene control, can help express tagged proteins at endogenous levels.

TextSentencer_T433

65664-65786

Sentence

denotes

Clearly, interaction proteomics just highlights one biological function of a given protein, i.e., its interaction network.

TextSentencer_T433

65664-65786

Sentence

denotes

Clearly, interaction proteomics just highlights one biological function of a given protein, i.e., its interaction network.

T67724

65664-65786

Sentence

denotes

Clearly, interaction proteomics just highlights one biological function of a given protein, i.e., its interaction network.

TextSentencer_T434

65787-65874

Sentence

denotes

Thus the method should be considered as complimentary tool in the virologist's toolbox.

TextSentencer_T434

65787-65874

Sentence

denotes

Thus the method should be considered as complimentary tool in the virologist's toolbox.

T81426

65787-65874

Sentence

denotes

Thus the method should be considered as complimentary tool in the virologist's toolbox.

TextSentencer_T435

65875-66074

Sentence

denotes

To address whether an interaction is critical for virus infection, follow up analysis using established (RNAi, inhibitors, dominant negative mutants) or newly developed techniques (CRISPR) is needed.

TextSentencer_T435

65875-66074

Sentence

denotes

To address whether an interaction is critical for virus infection, follow up analysis using established (RNAi, inhibitors, dominant negative mutants) or newly developed techniques (CRISPR) is needed.

T46367

65875-66074

Sentence

denotes

To address whether an interaction is critical for virus infection, follow up analysis using established (RNAi, inhibitors, dominant negative mutants) or newly developed techniques (CRISPR) is needed.

TextSentencer_T436

66075-66393

Sentence

denotes

Nonetheless, we believe that interaction proteomics will prove essential to model molecular networks during virus infection, assign critical nodes, generate and test hypotheses on the molecular function of the proteins in the network and thereby reveal essential host factors, which can be targeted by antiviral drugs.

TextSentencer_T436

66075-66393

Sentence

denotes

Nonetheless, we believe that interaction proteomics will prove essential to model molecular networks during virus infection, assign critical nodes, generate and test hypotheses on the molecular function of the proteins in the network and thereby reveal essential host factors, which can be targeted by antiviral drugs.

T48429

66075-66393

Sentence

denotes

Nonetheless, we believe that interaction proteomics will prove essential to model molecular networks during virus infection, assign critical nodes, generate and test hypotheses on the molecular function of the proteins in the network and thereby reveal essential host factors, which can be targeted by antiviral drugs.

TextSentencer_T437

66394-66531

Sentence

denotes

Genetic screens identified numerous virus receptors, but their actual binding to the respective virus has often not been formerly proven.

TextSentencer_T437

66394-66531

Sentence

denotes

Genetic screens identified numerous virus receptors, but their actual binding to the respective virus has often not been formerly proven.

T62047

66394-66531

Sentence

denotes

Genetic screens identified numerous virus receptors, but their actual binding to the respective virus has often not been formerly proven.

TextSentencer_T438

66532-66629

Sentence

denotes

Quantitative interaction proteomics approaches hold the promise of closing this gap of knowledge.

TextSentencer_T438

66532-66629

Sentence

denotes

Quantitative interaction proteomics approaches hold the promise of closing this gap of knowledge.

T35879

66532-66629

Sentence

denotes

Quantitative interaction proteomics approaches hold the promise of closing this gap of knowledge.

TextSentencer_T439

66630-66809

Sentence

denotes

Due to technological and computational developments in the past decade proteomics is now on par with genomics and allows high throughout comprehensive analyses of complex samples.

TextSentencer_T439

66630-66809

Sentence

denotes

Due to technological and computational developments in the past decade proteomics is now on par with genomics and allows high throughout comprehensive analyses of complex samples.

T39677

66630-66809

Sentence

denotes

Due to technological and computational developments in the past decade proteomics is now on par with genomics and allows high throughout comprehensive analyses of complex samples.

TextSentencer_T440

66810-66929

Sentence

denotes

Recently, a 96-well compatible and streamlined interaction proteomics protocol has been developed (Hosp et al., 2015) .

TextSentencer_T440

66810-66929

Sentence

denotes

Recently, a 96-well compatible and streamlined interaction proteomics protocol has been developed (Hosp et al., 2015) .

T8114

66810-66929

Sentence

denotes

Recently, a 96-well compatible and streamlined interaction proteomics protocol has been developed (Hosp et al., 2015) .

TextSentencer_T441

66930-67219

Sentence

denotes

Given the fact that for many viruses the target cells are either not known or are of multiple host and tissue origin, the parallel analysis of many biological samples will in the future allow proteomics screening approaches without prior knowledge of receptor expression or susceptibility.

TextSentencer_T441

66930-67219

Sentence

denotes

Given the fact that for many viruses the target cells are either not known or are of multiple host and tissue origin, the parallel analysis of many biological samples will in the future allow proteomics screening approaches without prior knowledge of receptor expression or susceptibility.

T43345

66930-67219

Sentence

denotes

Given the fact that for many viruses the target cells are either not known or are of multiple host and tissue origin, the parallel analysis of many biological samples will in the future allow proteomics screening approaches without prior knowledge of receptor expression or susceptibility.

TextSentencer_T442

67220-67396

Sentence

denotes

A second consequence of the vast increase in MS sensitivity is that patient material and material from animal experiments, which is typically limited, can be analyzed in depth.

TextSentencer_T442

67220-67396

Sentence

denotes

A second consequence of the vast increase in MS sensitivity is that patient material and material from animal experiments, which is typically limited, can be analyzed in depth.

T12755

67220-67396

Sentence

denotes

A second consequence of the vast increase in MS sensitivity is that patient material and material from animal experiments, which is typically limited, can be analyzed in depth.

TextSentencer_T443

67397-67523

Sentence

denotes

Transcriptomics data only accounts for a subset of pathogen induced changes in a host as it lacks information on PTMs and PPI.

TextSentencer_T443

67397-67523

Sentence

denotes

Transcriptomics data only accounts for a subset of pathogen induced changes in a host as it lacks information on PTMs and PPI.

T80723

67397-67523

Sentence

denotes

Transcriptomics data only accounts for a subset of pathogen induced changes in a host as it lacks information on PTMs and PPI.

TextSentencer_T444

67524-67666

Sentence

denotes

Proteomics of ex vivo samples thus holds the promise of providing a more complete picture of the virus host interplay in an infected organism.

TextSentencer_T444

67524-67666

Sentence

denotes

Proteomics of ex vivo samples thus holds the promise of providing a more complete picture of the virus host interplay in an infected organism.

T74049

67524-67666

Sentence

denotes

Proteomics of ex vivo samples thus holds the promise of providing a more complete picture of the virus host interplay in an infected organism.

TextSentencer_T445

67667-67832

Sentence

denotes

It will be interesting to demonstrate to what extend the changes in host and virus proteomes observed thus far in cell culture models, reflect the in vivo situation.

TextSentencer_T445

67667-67832

Sentence

denotes

It will be interesting to demonstrate to what extend the changes in host and virus proteomes observed thus far in cell culture models, reflect the in vivo situation.

T86247

67667-67832

Sentence

denotes

It will be interesting to demonstrate to what extend the changes in host and virus proteomes observed thus far in cell culture models, reflect the in vivo situation.

TextSentencer_T446

67833-68064

Sentence

denotes

Notably, proteomics can not only elucidate protein networks during virus infection, but also serve to identify diagnostic and prognostic markers of virus infection and disease progression (Mancone et al., 2013; Rhea et al., 2010) .

TextSentencer_T446

67833-68064

Sentence

denotes

Notably, proteomics can not only elucidate protein networks during virus infection, but also serve to identify diagnostic and prognostic markers of virus infection and disease progression (Mancone et al., 2013; Rhea et al., 2010) .

T10840

67833-68064

Sentence

denotes

Notably, proteomics can not only elucidate protein networks during virus infection, but also serve to identify diagnostic and prognostic markers of virus infection and disease progression (Mancone et al., 2013; Rhea et al., 2010) .

TextSentencer_T447

68065-68187

Sentence

denotes

It also allows the identification of targets of chemical compound libraries by interaction proteomics (Ong et al., 2009) .

TextSentencer_T447

68065-68187

Sentence

denotes

It also allows the identification of targets of chemical compound libraries by interaction proteomics (Ong et al., 2009) .

T18662

68065-68187

Sentence

denotes

It also allows the identification of targets of chemical compound libraries by interaction proteomics (Ong et al., 2009) .

TextSentencer_T448

68188-68300

Sentence

denotes

MS-based proteomics is thus valuable for virologists with a molecular biology, cell biology, and clinical focus.

TextSentencer_T448

68188-68300

Sentence

denotes

MS-based proteomics is thus valuable for virologists with a molecular biology, cell biology, and clinical focus.

T7047

68188-68300

Sentence

denotes

MS-based proteomics is thus valuable for virologists with a molecular biology, cell biology, and clinical focus.

TextSentencer_T449

68301-68569

Sentence

denotes

We believe that increasing availability of proteomics hardware, protocols and analysis software is currently spurring a shift from the largely genomics dominated field of virus infection research towards proteomic characterization of cellular perturbations by viruses.

TextSentencer_T449

68301-68569

Sentence

denotes

We believe that increasing availability of proteomics hardware, protocols and analysis software is currently spurring a shift from the largely genomics dominated field of virus infection research towards proteomic characterization of cellular perturbations by viruses.

T85793

68301-68569

Sentence

denotes

We believe that increasing availability of proteomics hardware, protocols and analysis software is currently spurring a shift from the largely genomics dominated field of virus infection research towards proteomic characterization of cellular perturbations by viruses.

CORD-19:08cb9d14d2fa21a6153a9922d4ad896b992c88c2 JSON TXT 11 Projects

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CORD-19:08cb9d14d2fa21a6153a9922d4ad896b992c88c2 JSONTXT 11 Projects

Annnotations TAB TSV DIC JSON TextAE

CORD-19:08cb9d14d2fa21a6153a9922d4ad896b992c88c2 JSON TXT 11 Projects