CORD-19-Sentences  

CORD-19:9dc436e46261781fe2991baeff4ddc7dd2e96c9b JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-50 Sentence denotes Cryo-EM Studies of Virus-Antibody Immune Complexes
TextSentencer_T1 0-50 Sentence denotes Cryo-EM Studies of Virus-Antibody Immune Complexes
TextSentencer_T2 52-60 Sentence denotes Abstract
TextSentencer_T2 52-60 Sentence denotes Abstract
TextSentencer_T3 61-193 Sentence denotes Antibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools.
TextSentencer_T3 61-193 Sentence denotes Antibodies play critical roles in neutralizing viral infections and are increasingly used as therapeutic drugs and diagnostic tools.
TextSentencer_T4 194-421 Sentence denotes Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design.
TextSentencer_T4 194-421 Sentence denotes Structural studies on virus-antibody immune complexes are important for better understanding the molecular mechanisms of antibody-mediated neutralization and also provide valuable information for structure-based vaccine design.
TextSentencer_T5 422-555 Sentence denotes Cryo-electron microscopy (cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes.
TextSentencer_T5 422-555 Sentence denotes Cryo-electron microscopy (cryo-EM) has recently matured as a powerful structural technique for studying bio-macromolecular complexes.
TextSentencer_T6 556-743 Sentence denotes When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies.
TextSentencer_T6 556-743 Sentence denotes When combined with X-ray crystallography, cryo-EM provides a routine approach for structurally characterizing the immune complexes formed between icosahedral viruses and their antibodies.
TextSentencer_T7 744-1035 Sentence denotes In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3 (picornaviruses) and T = 3 (flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states.
TextSentencer_T7 744-1035 Sentence denotes In this review, recent advances in the structural understanding of virus-antibody interactions are outlined for whole virions with icosahedral T = pseudo 3 (picornaviruses) and T = 3 (flaviviruses) architectures, focusing on the dynamic nature of viral shells in different functional states.
TextSentencer_T8 1036-1140 Sentence denotes Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens.
TextSentencer_T8 1036-1140 Sentence denotes Glycoprotein complexes from pleomorphic enveloped viruses are also discussed as immune complex antigens.
TextSentencer_T9 1141-1293 Sentence denotes Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.
TextSentencer_T9 1141-1293 Sentence denotes Improving our understanding of viral epitope structures using virus-based platforms would provide a fundamental road map for future vaccine development.
TextSentencer_T10 1295-1403 Sentence denotes Antibodies, the essential components of humoral immunity, are a major defense line against viral infections.
TextSentencer_T10 1295-1403 Sentence denotes Antibodies, the essential components of humoral immunity, are a major defense line against viral infections.
TextSentencer_T11 1404-1524 Sentence denotes To neutralize viral infections, antibodies primarily bind to specific epitopes on the outer surfaces of viral particles.
TextSentencer_T11 1404-1524 Sentence denotes To neutralize viral infections, antibodies primarily bind to specific epitopes on the outer surfaces of viral particles.
TextSentencer_T12 1525-1721 Sentence denotes An important first step in modern structural vaccinology involves structurally characterizing the interactions occurring between viral antigens and their cognate antibodies (Anasir and Poh 2019) .
TextSentencer_T12 1525-1721 Sentence denotes An important first step in modern structural vaccinology involves structurally characterizing the interactions occurring between viral antigens and their cognate antibodies (Anasir and Poh 2019) .
TextSentencer_T13 1722-1866 Sentence denotes This step provides the direct evidence for the location of viral epitopes, which helps to elucidate the neutralization mechanisms of antibodies.
TextSentencer_T13 1722-1866 Sentence denotes This step provides the direct evidence for the location of viral epitopes, which helps to elucidate the neutralization mechanisms of antibodies.
TextSentencer_T14 1867-2013 Sentence denotes The first high-resolution structure of a virus (tomato bushy stunt virus) was solved four decades ago using X-ray crystallography (Harrison et al.
TextSentencer_T14 1867-2013 Sentence denotes The first high-resolution structure of a virus (tomato bushy stunt virus) was solved four decades ago using X-ray crystallography (Harrison et al.
TextSentencer_T15 2014-2198 Sentence denotes 1978) , a technique that has been primarily limited to determining the structures of relatively simple non-enveloped viruses (http://viperdb. scripps.edu/xray.php) or viral components.
TextSentencer_T15 2014-2198 Sentence denotes 1978) , a technique that has been primarily limited to determining the structures of relatively simple non-enveloped viruses (http://viperdb. scripps.edu/xray.php) or viral components.
TextSentencer_T16 2199-2455 Sentence denotes Because crystallizing virus-antibody complexes can be challenging, morphological studies of virus-antibody interactions have long been carried out through transmission electron microscopy (TEM) with negative staining protocols (Almeida and Waterson 1969) .
TextSentencer_T16 2199-2455 Sentence denotes Because crystallizing virus-antibody complexes can be challenging, morphological studies of virus-antibody interactions have long been carried out through transmission electron microscopy (TEM) with negative staining protocols (Almeida and Waterson 1969) .
TextSentencer_T17 2456-2633 Sentence denotes The resolution achieved by this technique is usually low, but the structural details can be enhanced by modeling high-resolution crystal structures into low-resolution TEM maps.
TextSentencer_T17 2456-2633 Sentence denotes The resolution achieved by this technique is usually low, but the structural details can be enhanced by modeling high-resolution crystal structures into low-resolution TEM maps.
TextSentencer_T18 2634-2840 Sentence denotes As the negatively-stained samples are visualizable with a conventional TEM instrument, they are still widely used today for characterizing immune complexes with human viruses like influenza A (Ekiert et al.
TextSentencer_T18 2634-2840 Sentence denotes As the negatively-stained samples are visualizable with a conventional TEM instrument, they are still widely used today for characterizing immune complexes with human viruses like influenza A (Ekiert et al.
TextSentencer_T19 2841-2870 Sentence denotes 2012) , Marburg (Flyak et al.
TextSentencer_T19 2841-2870 Sentence denotes 2012) , Marburg (Flyak et al.
TextSentencer_T20 2871-2908 Sentence denotes 2015) and Ebola viruses (Flyak et al.
TextSentencer_T20 2871-2908 Sentence denotes 2015) and Ebola viruses (Flyak et al.
TextSentencer_T21 2909-2916 Sentence denotes 2016) .
TextSentencer_T21 2909-2916 Sentence denotes 2016) .
TextSentencer_T22 2917-3093 Sentence denotes Cryo-electron microscopy (cryo-EM), a Nobelprize-winning technique, is now routinely used for studying virus-antibody complexes at high resolution (Earl and Subramaniam 2016) .
TextSentencer_T22 2917-3093 Sentence denotes Cryo-electron microscopy (cryo-EM), a Nobelprize-winning technique, is now routinely used for studying virus-antibody complexes at high resolution (Earl and Subramaniam 2016) .
TextSentencer_T23 3094-3398 Sentence denotes In contrast to negatively-stained samples, which might be significantly distorted by the dehydration process and the presence of stains, virus particles in cryo-EM studies are freshly frozen in a thin layer of vitreous ice to maintain their native conformations, making high-resolution analyses possible.
TextSentencer_T23 3094-3398 Sentence denotes In contrast to negatively-stained samples, which might be significantly distorted by the dehydration process and the presence of stains, virus particles in cryo-EM studies are freshly frozen in a thin layer of vitreous ice to maintain their native conformations, making high-resolution analyses possible.
TextSentencer_T24 3399-3663 Sentence denotes However, before direct electron detection cameras (DEDs) were introduced in 2012, cryo-EM structures could only be solved at subnanometer resolutions with traditional CCD cameras, except some pioneer work based on images recorded on photographic film (Zhang et al.
TextSentencer_T24 3399-3663 Sentence denotes However, before direct electron detection cameras (DEDs) were introduced in 2012, cryo-EM structures could only be solved at subnanometer resolutions with traditional CCD cameras, except some pioneer work based on images recorded on photographic film (Zhang et al.
TextSentencer_T25 3664-3671 Sentence denotes 2010) .
TextSentencer_T25 3664-3671 Sentence denotes 2010) .
TextSentencer_T26 3672-3917 Sentence denotes Largely resulting from the development of DED technologies, better microscopes and sophisticated reconstruction algorithms, cryo-EM has developed in recent years as a powerful highresolution technique in structural biology research (Shen 2018) .
TextSentencer_T26 3672-3917 Sentence denotes Largely resulting from the development of DED technologies, better microscopes and sophisticated reconstruction algorithms, cryo-EM has developed in recent years as a powerful highresolution technique in structural biology research (Shen 2018) .
TextSentencer_T27 3918-4053 Sentence denotes There are two major 3D cryo-EM analysis strategies: single particle analysis (SPA) and cryo-electron tomography (cryo-ET) (Danev et al.
TextSentencer_T27 3918-4053 Sentence denotes There are two major 3D cryo-EM analysis strategies: single particle analysis (SPA) and cryo-electron tomography (cryo-ET) (Danev et al.
TextSentencer_T28 4054-4061 Sentence denotes 2019) .
TextSentencer_T28 4054-4061 Sentence denotes 2019) .
TextSentencer_T29 4062-4162 Sentence denotes SPA is usually used for macromolecular assemblies that are stable, soluble and homogeneous in vitro.
TextSentencer_T29 4062-4162 Sentence denotes SPA is usually used for macromolecular assemblies that are stable, soluble and homogeneous in vitro.
TextSentencer_T30 4163-4459 Sentence denotes Because some viruses are highly structurally ordered, especially those with icosahedral symmetries, it is possible to solve the structures of whole viral particles at better than 3 Å resolution using SPA by combining data from several thousands of purified virus particles (Jiang and Tang 2017) .
TextSentencer_T30 4163-4459 Sentence denotes Because some viruses are highly structurally ordered, especially those with icosahedral symmetries, it is possible to solve the structures of whole viral particles at better than 3 Å resolution using SPA by combining data from several thousands of purified virus particles (Jiang and Tang 2017) .
TextSentencer_T31 4460-4540 Sentence denotes The density maps at this resolution allow the de novo building of atomic models.
TextSentencer_T31 4460-4540 Sentence denotes The density maps at this resolution allow the de novo building of atomic models.
TextSentencer_T32 4541-4684 Sentence denotes For viruses with pleomorphic shapes, 3D reconstruction of a single vitrified virion is achievable using cryo-ET procedures at *25-Å resolution.
TextSentencer_T32 4541-4684 Sentence denotes For viruses with pleomorphic shapes, 3D reconstruction of a single vitrified virion is achievable using cryo-ET procedures at *25-Å resolution.
TextSentencer_T33 4685-4854 Sentence denotes Sub-tomogram averaging techniques are further exploitable for achieving better structural details for repeating structures, such as the surface glycoproteins on viruses.
TextSentencer_T33 4685-4854 Sentence denotes Sub-tomogram averaging techniques are further exploitable for achieving better structural details for repeating structures, such as the surface glycoproteins on viruses.
TextSentencer_T34 4855-5031 Sentence denotes Both SPA and cryo-ET approaches have been used for structural studies on the interactions occurring between whole virions (or viral components) and their associated antibodies.
TextSentencer_T34 4855-5031 Sentence denotes Both SPA and cryo-ET approaches have been used for structural studies on the interactions occurring between whole virions (or viral components) and their associated antibodies.
TextSentencer_T35 5032-5106 Sentence denotes Antibody molecules for cryo-EM studies can be generated in different ways.
TextSentencer_T35 5032-5106 Sentence denotes Antibody molecules for cryo-EM studies can be generated in different ways.
TextSentencer_T36 5107-5373 Sentence denotes Mass production of murine monoclonal antibodies (mAbs) has traditionally been achieved by the use of hybridoma technology where antibody-producing B cells derived from immunized mice are fused to an immortalized cell line (e.g., myeloma) (Kohler and Milstein 1975) .
TextSentencer_T36 5107-5373 Sentence denotes Mass production of murine monoclonal antibodies (mAbs) has traditionally been achieved by the use of hybridoma technology where antibody-producing B cells derived from immunized mice are fused to an immortalized cell line (e.g., myeloma) (Kohler and Milstein 1975) .
TextSentencer_T37 5374-5558 Sentence denotes Recombinant antibodies can be generated by phage display technology followed by in vitro selection, which targets the whole virus particles or some viral components (Hoogenboom 2005) .
TextSentencer_T37 5374-5558 Sentence denotes Recombinant antibodies can be generated by phage display technology followed by in vitro selection, which targets the whole virus particles or some viral components (Hoogenboom 2005) .
TextSentencer_T38 5559-5673 Sentence denotes Various methods for isolating antigen-specific human B cells to obtain mAbs have also been reported (Crowe 2017) .
TextSentencer_T38 5559-5673 Sentence denotes Various methods for isolating antigen-specific human B cells to obtain mAbs have also been reported (Crowe 2017) .
TextSentencer_T39 5674-5966 Sentence denotes For viruses with naturally occurring high mutation rates like HIV-1, broadly neutralizing antibodies (bNAbs) that potently target a wide range of viral strains have been isolated from virus-infected individuals and extensively studied using cryo-EM (Stephenson and Barouch 2016; Chuang et al.
TextSentencer_T39 5674-5966 Sentence denotes For viruses with naturally occurring high mutation rates like HIV-1, broadly neutralizing antibodies (bNAbs) that potently target a wide range of viral strains have been isolated from virus-infected individuals and extensively studied using cryo-EM (Stephenson and Barouch 2016; Chuang et al.
TextSentencer_T40 5967-5974 Sentence denotes 2019) .
TextSentencer_T40 5967-5974 Sentence denotes 2019) .
TextSentencer_T41 5975-6064 Sentence denotes For cryo-EM analyses, the antibody components are IgG molecules or their truncated parts.
TextSentencer_T41 5975-6064 Sentence denotes For cryo-EM analyses, the antibody components are IgG molecules or their truncated parts.
TextSentencer_T42 6065-6294 Sentence denotes In a single IgG molecule, two antigen binding fragments (Fabs) are present (Fig. 1A , 1B), a situation that could result in highly heterogeneous antigen-antibody complexes if one antigen particle becomes crosslinked with another.
TextSentencer_T42 6065-6294 Sentence denotes In a single IgG molecule, two antigen binding fragments (Fabs) are present (Fig. 1A , 1B), a situation that could result in highly heterogeneous antigen-antibody complexes if one antigen particle becomes crosslinked with another.
TextSentencer_T43 6295-6345 Sentence denotes Except for SPA studies on IgG bivalency (Ye et al.
TextSentencer_T43 6295-6345 Sentence denotes Except for SPA studies on IgG bivalency (Ye et al.
TextSentencer_T44 6346-6436 Sentence denotes 2016) , IgG is usually used in cryo-ET studies at medium resolution for HIV-1 (Tran et al.
TextSentencer_T44 6346-6436 Sentence denotes 2016) , IgG is usually used in cryo-ET studies at medium resolution for HIV-1 (Tran et al.
TextSentencer_T45 6437-6467 Sentence denotes 2012) , influenza (Tran et al.
TextSentencer_T45 6437-6467 Sentence denotes 2012) , influenza (Tran et al.
TextSentencer_T46 6468-6505 Sentence denotes 2016b) and Ebola viruses (Tran et al.
TextSentencer_T46 6468-6505 Sentence denotes 2016b) and Ebola viruses (Tran et al.
TextSentencer_T47 6506-6514 Sentence denotes 2016a) .
TextSentencer_T47 6506-6514 Sentence denotes 2016a) .
TextSentencer_T48 6515-6727 Sentence denotes Compared with the intact IgG molecule, the monovalent Fab fragments generated by papain digestion of whole IgG molecules are more commonly used for structural studies on virus-antibody complexes (Tables 1, 2, 3).
TextSentencer_T48 6515-6727 Sentence denotes Compared with the intact IgG molecule, the monovalent Fab fragments generated by papain digestion of whole IgG molecules are more commonly used for structural studies on virus-antibody complexes (Tables 1, 2, 3).
TextSentencer_T49 6728-6903 Sentence denotes The single-chain variable fragment (scFv) generated by fusing the variable regions of the heavy (V H ) to the light (V L ) chains with a flexible peptide linker (Finlay et al.
TextSentencer_T49 6728-6903 Sentence denotes The single-chain variable fragment (scFv) generated by fusing the variable regions of the heavy (V H ) to the light (V L ) chains with a flexible peptide linker (Finlay et al.
TextSentencer_T50 6904-6983 Sentence denotes 2017) can be used for cryo-EM studies of virus-antibody interactions Liu et al.
TextSentencer_T50 6904-6983 Sentence denotes 2017) can be used for cryo-EM studies of virus-antibody interactions Liu et al.
TextSentencer_T51 6984-6991 Sentence denotes 2017) .
TextSentencer_T51 6984-6991 Sentence denotes 2017) .
TextSentencer_T52 6992-7239 Sentence denotes Single-domain antibodies (sdAbs), such as variable domains of heavy chain-only antibodies (termed VHH) and V H domains of human IgG molecules, have also served as antibody derivatives for cryo-ET studies when combined with sub-tomogram averaging .
TextSentencer_T52 6992-7239 Sentence denotes Single-domain antibodies (sdAbs), such as variable domains of heavy chain-only antibodies (termed VHH) and V H domains of human IgG molecules, have also served as antibody derivatives for cryo-ET studies when combined with sub-tomogram averaging .
TextSentencer_T53 7240-7398 Sentence denotes Thus far, 3D reconstructions of virus-Fab complexes at atomic resolution are available for some picornaviruses, including rhinovirus B14 (RV-B14) (Dong et al.
TextSentencer_T53 7240-7398 Sentence denotes Thus far, 3D reconstructions of virus-Fab complexes at atomic resolution are available for some picornaviruses, including rhinovirus B14 (RV-B14) (Dong et al.
TextSentencer_T54 7399-7414 Sentence denotes 2017 Table 1 ).
TextSentencer_T54 7399-7414 Sentence denotes 2017 Table 1 ).
TextSentencer_T55 7415-7524 Sentence denotes The atomic models of the capsid protein were well-fitted in the cryo-EM density map for HPeV3 (Fig. 1C, 1D) .
TextSentencer_T55 7415-7524 Sentence denotes The atomic models of the capsid protein were well-fitted in the cryo-EM density map for HPeV3 (Fig. 1C, 1D) .
TextSentencer_T56 7525-7605 Sentence denotes Nevertheless, only the V H and V L domains have clearly defined densities (Figs.
TextSentencer_T56 7525-7605 Sentence denotes Nevertheless, only the V H and V L domains have clearly defined densities (Figs.
TextSentencer_T57 7606-7819 Sentence denotes 1E, 2G), whereas the density regions in the C H1 and C L domains are less ordered, reflecting the flexibility of the linker regions between the constant domains (C H1 and C L ) and variable domains (V H and V L ).
TextSentencer_T57 7606-7819 Sentence denotes 1E, 2G), whereas the density regions in the C H1 and C L domains are less ordered, reflecting the flexibility of the linker regions between the constant domains (C H1 and C L ) and variable domains (V H and V L ).
TextSentencer_T58 7820-8062 Sentence denotes Because the antigen binding site is determined by six hypervariable loops, namely, the complementarity-determining regions (CDRs) on the V H and V L domains, these densities can provide detailed information about the virus-antibody interface.
TextSentencer_T58 7820-8062 Sentence denotes Because the antigen binding site is determined by six hypervariable loops, namely, the complementarity-determining regions (CDRs) on the V H and V L domains, these densities can provide detailed information about the virus-antibody interface.
TextSentencer_T59 8063-8312 Sentence denotes Based on high-resolution structural analysis, CDRs from five HAV antibodies (R10, F4, F6, F7 and F9) interact with a single conserved antigenic site, which has been shown as an attractive target for rational development of antiviral drugs Cao et al.
TextSentencer_T59 8063-8312 Sentence denotes Based on high-resolution structural analysis, CDRs from five HAV antibodies (R10, F4, F6, F7 and F9) interact with a single conserved antigenic site, which has been shown as an attractive target for rational development of antiviral drugs Cao et al.
TextSentencer_T60 8313-8320 Sentence denotes 2019) .
TextSentencer_T60 8313-8320 Sentence denotes 2019) .
TextSentencer_T61 8321-8468 Sentence denotes Viruses with icosahedral capsid shells are the most studied antigens in immune complexes by cryo-EM techniques, largely due to their high symmetry.
TextSentencer_T61 8321-8468 Sentence denotes Viruses with icosahedral capsid shells are the most studied antigens in immune complexes by cryo-EM techniques, largely due to their high symmetry.
TextSentencer_T62 8469-8620 Sentence denotes Since perfect symmetry could be broken as observed in many situations, such as symmetry mismatches at the portal vertex of herpesviruses (Parent et al.
TextSentencer_T62 8469-8620 Sentence denotes Since perfect symmetry could be broken as observed in many situations, such as symmetry mismatches at the portal vertex of herpesviruses (Parent et al.
TextSentencer_T63 8621-8701 Sentence denotes 2018 ) and partially mature particles of dengue viruses (Rodenhuis-Zybert et al.
TextSentencer_T63 8621-8701 Sentence denotes 2018 ) and partially mature particles of dengue viruses (Rodenhuis-Zybert et al.
TextSentencer_T64 8702-8877 Sentence denotes 2011), block-based or localized reconstruction strategies are now often applied to icosahedral particles showing conformational flexibility or symmetry mismatches (Ilca et al.
TextSentencer_T64 8702-8877 Sentence denotes 2011), block-based or localized reconstruction strategies are now often applied to icosahedral particles showing conformational flexibility or symmetry mismatches (Ilca et al.
TextSentencer_T65 8878-8885 Sentence denotes 2015; .
TextSentencer_T65 8878-8885 Sentence denotes 2015; .
TextSentencer_T66 8886-9014 Sentence denotes Geometrically, an icosahedral object has 60 equivalent positions related by fivefold, threefold and twofold rotational symmetry.
TextSentencer_T66 8886-9014 Sentence denotes Geometrically, an icosahedral object has 60 equivalent positions related by fivefold, threefold and twofold rotational symmetry.
TextSentencer_T67 9015-9115 Sentence denotes The 60 repeating units occupying each of these positions are referred to as asymmetric units (ASUs).
TextSentencer_T67 9015-9115 Sentence denotes The 60 repeating units occupying each of these positions are referred to as asymmetric units (ASUs).
TextSentencer_T68 9116-9244 Sentence denotes The triangulation number (or T-number) is usually assigned to an icosahedral virus to identify the number of subunits in an ASU.
TextSentencer_T68 9116-9244 Sentence denotes The triangulation number (or T-number) is usually assigned to an icosahedral virus to identify the number of subunits in an ASU.
TextSentencer_T69 9245-9427 Sentence denotes In the simplest T = 1 virus (e.g., parvoviruses), only one capsid molecule is present in the ASU, and the 60 capsid protein copies form an enclosed shell to protect the viral genome.
TextSentencer_T69 9245-9427 Sentence denotes In the simplest T = 1 virus (e.g., parvoviruses), only one capsid molecule is present in the ASU, and the 60 capsid protein copies form an enclosed shell to protect the viral genome.
TextSentencer_T70 9428-9693 Sentence denotes In contrast, in a T = 3 virus (e.g., flaviviruses), the ASU consists of three chemically identical capsid proteins (e.g., the E protein from flaviviruses), each of which undergoes conformational adjustments to occupy three ''quasi-equivalent'' positions in the ASU.
TextSentencer_T70 9428-9693 Sentence denotes In contrast, in a T = 3 virus (e.g., flaviviruses), the ASU consists of three chemically identical capsid proteins (e.g., the E protein from flaviviruses), each of which undergoes conformational adjustments to occupy three ''quasi-equivalent'' positions in the ASU.
TextSentencer_T71 9694-9746 Sentence denotes Some icosahedral viruses show ''pseudo'' T geometry.
TextSentencer_T71 9694-9746 Sentence denotes Some icosahedral viruses show ''pseudo'' T geometry.
TextSentencer_T72 9747-9881 Sentence denotes Picornaviruses (T = pseudo 3) have an ASU of three capsid protein types (VP1, VP2 and VP3), possibly making them a special T = 1 case.
TextSentencer_T72 9747-9881 Sentence denotes Picornaviruses (T = pseudo 3) have an ASU of three capsid protein types (VP1, VP2 and VP3), possibly making them a special T = 1 case.
TextSentencer_T73 9882-10047 Sentence denotes Next, we will examine the epitope distribution on these two types of humaninfection viruses, and also discuss the binding capacity of Fab molecules on their virions.
TextSentencer_T73 9882-10047 Sentence denotes Next, we will examine the epitope distribution on these two types of humaninfection viruses, and also discuss the binding capacity of Fab molecules on their virions.
TextSentencer_T74 10048-10217 Sentence denotes Small non-enveloped viruses in the Picornaviridae family cause mild or severe human infections, and provide important antigenic particles for cryo-EM studies (Table 1) .
TextSentencer_T74 10048-10217 Sentence denotes Small non-enveloped viruses in the Picornaviridae family cause mild or severe human infections, and provide important antigenic particles for cryo-EM studies (Table 1) .
TextSentencer_T75 10218-10267 Sentence denotes Crystal structures of rhinovirus (Rossmann et al.
TextSentencer_T75 10218-10267 Sentence denotes Crystal structures of rhinovirus (Rossmann et al.
TextSentencer_T76 10268-10302 Sentence denotes 1985) and poliovirus (Hogle et al.
TextSentencer_T76 10268-10302 Sentence denotes 1985) and poliovirus (Hogle et al.
TextSentencer_T77 10303-10473 Sentence denotes 1985) have revealed that on the icosahedral capsid shell, VP1 lies close to fivefold axes and the neighboring VP2 and VP3 are found around threefold axes ( Fig. 2A, 2B ).
TextSentencer_T77 10303-10473 Sentence denotes 1985) have revealed that on the icosahedral capsid shell, VP1 lies close to fivefold axes and the neighboring VP2 and VP3 are found around threefold axes ( Fig. 2A, 2B ).
TextSentencer_T78 10474-10614 Sentence denotes Since 1997, outbreaks of hand-foot-and-mouth disease have been increasingly reported, the leading pathogens of which are various (Table 2 ).
TextSentencer_T78 10474-10614 Sentence denotes Since 1997, outbreaks of hand-foot-and-mouth disease have been increasingly reported, the leading pathogens of which are various (Table 2 ).
TextSentencer_T79 10615-10813 Sentence denotes In contrast with non-enveloped enteroviruses, flaviviruses possess host-derived lipid bilayers with 180 pairs of envelope (E) and membrane (M) proteins on the viral membrane (Perera and Kuhn 2008) .
TextSentencer_T79 10615-10813 Sentence denotes In contrast with non-enveloped enteroviruses, flaviviruses possess host-derived lipid bilayers with 180 pairs of envelope (E) and membrane (M) proteins on the viral membrane (Perera and Kuhn 2008) .
TextSentencer_T80 10814-10987 Sentence denotes Organized as head-totail homodimers on the outer surface (Fig. 2C, 2D) , the E protein plays important roles in receptor binding and in mediating virus-host membrane fusion.
TextSentencer_T80 10814-10987 Sentence denotes Organized as head-totail homodimers on the outer surface (Fig. 2C, 2D) , the E protein plays important roles in receptor binding and in mediating virus-host membrane fusion.
TextSentencer_T81 10988-11110 Sentence denotes Compared with picornaviruses, flavivirus epitopes do not possess an apparent pattern near symmetrical axes (Fig. 2I, 2J ).
TextSentencer_T81 10988-11110 Sentence denotes Compared with picornaviruses, flavivirus epitopes do not possess an apparent pattern near symmetrical axes (Fig. 2I, 2J ).
TextSentencer_T82 11111-11231 Sentence denotes Based on how Fab interacts with the E dimer, different epitopes on the DENV E protein are classifiable into four groups:
TextSentencer_T82 11111-11231 Sentence denotes Based on how Fab interacts with the E dimer, different epitopes on the DENV E protein are classifiable into four groups:
TextSentencer_T83 11232-11303 Sentence denotes (1) those that occur within an E monomer (e.g., 1F4) (Fibriansah et al.
TextSentencer_T83 11232-11303 Sentence denotes (1) those that occur within an E monomer (e.g., 1F4) (Fibriansah et al.
TextSentencer_T84 11304-11423 Sentence denotes 2014 ); (2) those spanning the adjacent surface of two E molecules from neighboring E dimers (e.g., 14c10) (Teoh et al.
TextSentencer_T84 11304-11423 Sentence denotes 2014 ); (2) those spanning the adjacent surface of two E molecules from neighboring E dimers (e.g., 14c10) (Teoh et al.
TextSentencer_T85 11424-11557 Sentence denotes 2012) ; (3) those consisting of amino acid residues from the two E molecules within an E dimer (e.g., 747(4)B7) (Dejnirattisai et al.
TextSentencer_T85 11424-11557 Sentence denotes 2012) ; (3) those consisting of amino acid residues from the two E molecules within an E dimer (e.g., 747(4)B7) (Dejnirattisai et al.
TextSentencer_T86 11558-11658 Sentence denotes 2015) ; and (4) those that occur across three neighboring E molecules (e.g., 5J7) (Fibriansah et al.
TextSentencer_T86 11558-11658 Sentence denotes 2015) ; and (4) those that occur across three neighboring E molecules (e.g., 5J7) (Fibriansah et al.
TextSentencer_T87 11659-11667 Sentence denotes 2015b) .
TextSentencer_T87 11659-11667 Sentence denotes 2015b) .
TextSentencer_T88 11668-11833 Sentence denotes Largely based on antibody-E complex crystal structures, antibodies may target DI domain, DII fusion loop epitope (FLE) or DIII domain within an E monomer (Dai et al.
TextSentencer_T88 11668-11833 Sentence denotes Largely based on antibody-E complex crystal structures, antibodies may target DI domain, DII fusion loop epitope (FLE) or DIII domain within an E monomer (Dai et al.
TextSentencer_T89 11834-11841 Sentence denotes 2016) .
TextSentencer_T89 11834-11841 Sentence denotes 2016) .
TextSentencer_T90 11842-11949 Sentence denotes The distance between neighboring epitopes can impact the number of bound antibody molecules on each virion.
TextSentencer_T90 11842-11949 Sentence denotes The distance between neighboring epitopes can impact the number of bound antibody molecules on each virion.
TextSentencer_T91 11950-12144 Sentence denotes Although both MA28-7 and 1D5 Fabs bind to site 1 of picornaviruses, only one MA28-7 Fab fragment occupies each fivefold vertex ) while five 1D5 Fab molecules bind each fivefold vertex of CV-A6 .
TextSentencer_T91 11950-12144 Sentence denotes Although both MA28-7 and 1D5 Fabs bind to site 1 of picornaviruses, only one MA28-7 Fab fragment occupies each fivefold vertex ) while five 1D5 Fab molecules bind each fivefold vertex of CV-A6 .
TextSentencer_T92 12145-12303 Sentence denotes Compared with 1D5, Fab MA28-7 is closer to the symmetry axis, which renders steric hindrance between possible Fabs, thereby limiting the number of bound Fabs.
TextSentencer_T92 12145-12303 Sentence denotes Compared with 1D5, Fab MA28-7 is closer to the symmetry axis, which renders steric hindrance between possible Fabs, thereby limiting the number of bound Fabs.
TextSentencer_T93 12304-12622 Sentence denotes As another example, the bivalent binding pattern of D5 was characterized in which the two Fab IgG fragments could bind to the GH loops of neighboring VP1 molecules related by twofold symmetry, a finding consistent with the observation that D5 IgG was able to neutralize EV-A71 much more potently than D5 Fab (Ye et al.
TextSentencer_T93 12304-12622 Sentence denotes As another example, the bivalent binding pattern of D5 was characterized in which the two Fab IgG fragments could bind to the GH loops of neighboring VP1 molecules related by twofold symmetry, a finding consistent with the observation that D5 IgG was able to neutralize EV-A71 much more potently than D5 Fab (Ye et al.
TextSentencer_T94 12623-12630 Sentence denotes 2016) .
TextSentencer_T94 12623-12630 Sentence denotes 2016) .
TextSentencer_T95 12631-12781 Sentence denotes Contrastingly, the 22A12 binding sites near twofold axes on EV-A71 are further apart and bivalent binding of an antibody cannot occur (Shingler et al.
TextSentencer_T95 12631-12781 Sentence denotes Contrastingly, the 22A12 binding sites near twofold axes on EV-A71 are further apart and bivalent binding of an antibody cannot occur (Shingler et al.
TextSentencer_T96 12782-12789 Sentence denotes 2015) .
TextSentencer_T96 12782-12789 Sentence denotes 2015) .
TextSentencer_T97 12790-12906 Sentence denotes In some cases, Fab binding can even change the local arrangement of the E protein to accommodate more Fab molecules.
TextSentencer_T97 12790-12906 Sentence denotes In some cases, Fab binding can even change the local arrangement of the E protein to accommodate more Fab molecules.
TextSentencer_T98 12907-13062 Sentence denotes For example, when the total 180 copies of Fab ZKA190 bind to the ZIKV surface, E proteins at the fivefold vertices move apart and steric clash is avoided .
TextSentencer_T98 12907-13062 Sentence denotes For example, when the total 180 copies of Fab ZKA190 bind to the ZIKV surface, E proteins at the fivefold vertices move apart and steric clash is avoided .
TextSentencer_T99 13063-13186 Sentence denotes Structural variations in the capsid protein at quasiequivalent positions may also impact the number of bound Fab molecules.
TextSentencer_T99 13063-13186 Sentence denotes Structural variations in the capsid protein at quasiequivalent positions may also impact the number of bound Fab molecules.
TextSentencer_T100 13187-13287 Sentence denotes Within an ASU, the DENV E protein exists as three conformations showing slight structural variation.
TextSentencer_T100 13187-13287 Sentence denotes Within an ASU, the DENV E protein exists as three conformations showing slight structural variation.
TextSentencer_T101 13288-13371 Sentence denotes 180 copies of Fab 747(4)B7 in total can bind to a DENV virion (Dejnirattisai et al.
TextSentencer_T101 13288-13371 Sentence denotes 180 copies of Fab 747(4)B7 in total can bind to a DENV virion (Dejnirattisai et al.
TextSentencer_T102 13372-13451 Sentence denotes 2015) , suggesting that such variations have no apparent impact on the epitope.
TextSentencer_T102 13372-13451 Sentence denotes 2015) , suggesting that such variations have no apparent impact on the epitope.
TextSentencer_T103 13452-13539 Sentence denotes However, in other cases, conformational changes can result in a less effective epitope.
TextSentencer_T103 13452-13539 Sentence denotes However, in other cases, conformational changes can result in a less effective epitope.
TextSentencer_T104 13540-13784 Sentence denotes For example, Fab 1F4 (targeting the DI and DI-DII hinges) does not bind to the E proteins near the threefold vertices where the epitope is partially hidden; consequently, only 120 copies of Fab 1F4 interact with a DENV virion (Fibriansah et al.
TextSentencer_T104 13540-13784 Sentence denotes For example, Fab 1F4 (targeting the DI and DI-DII hinges) does not bind to the E proteins near the threefold vertices where the epitope is partially hidden; consequently, only 120 copies of Fab 1F4 interact with a DENV virion (Fibriansah et al.
TextSentencer_T105 13785-13792 Sentence denotes 2014) .
TextSentencer_T105 13785-13792 Sentence denotes 2014) .
TextSentencer_T106 13793-14021 Sentence denotes Additionally, the capacity of Fab to bind onto a virus particle may not be straightforward when the binding sites are not fully occupied, as shown in the density analysis of ZIKV-117 Fab in a cryo-EM reconstruction (Hasan et al.
TextSentencer_T106 13793-14021 Sentence denotes Additionally, the capacity of Fab to bind onto a virus particle may not be straightforward when the binding sites are not fully occupied, as shown in the density analysis of ZIKV-117 Fab in a cryo-EM reconstruction (Hasan et al.
TextSentencer_T107 14022-14029 Sentence denotes 2017 ).
TextSentencer_T107 14022-14029 Sentence denotes 2017 ).
TextSentencer_T108 14030-14128 Sentence denotes Antibodies have been used to capture intermediate states in the assembly pathway of enteroviruses.
TextSentencer_T108 14030-14128 Sentence denotes Antibodies have been used to capture intermediate states in the assembly pathway of enteroviruses.
TextSentencer_T109 14129-14260 Sentence denotes There are two major enterovirus particles in infected host cells: empty procapsids (noninfectious) and mature virions (infectious).
TextSentencer_T109 14129-14260 Sentence denotes There are two major enterovirus particles in infected host cells: empty procapsids (noninfectious) and mature virions (infectious).
TextSentencer_T110 14261-14401 Sentence denotes Upon binding to cellular receptors, the native virions are converted into uncoated intermediates called A(altered)particles (Shingler et al.
TextSentencer_T110 14261-14401 Sentence denotes Upon binding to cellular receptors, the native virions are converted into uncoated intermediates called A(altered)particles (Shingler et al.
TextSentencer_T111 14402-14409 Sentence denotes 2013 ).
TextSentencer_T111 14402-14409 Sentence denotes 2013 ).
TextSentencer_T112 14410-14526 Sentence denotes Binding to the E18 antibody transforms infectious EV-A71 into A-particles and triggers genome release (Plevka et al.
TextSentencer_T112 14410-14526 Sentence denotes Binding to the E18 antibody transforms infectious EV-A71 into A-particles and triggers genome release (Plevka et al.
TextSentencer_T113 14527-14534 Sentence denotes 2014 ).
TextSentencer_T113 14527-14534 Sentence denotes 2014 ).
TextSentencer_T114 14535-14691 Sentence denotes Uniquely, CV-A6 A-particles are biochemically and structurally stable, which enabled the A-particle-Fab complex to be reconstructed at a 3.8-Å resolution ).
TextSentencer_T114 14535-14691 Sentence denotes Uniquely, CV-A6 A-particles are biochemically and structurally stable, which enabled the A-particle-Fab complex to be reconstructed at a 3.8-Å resolution ).
TextSentencer_T115 14692-14893 Sentence denotes 2G8 shows cross-reactivity against the CV-A10 procapsid, the mature virion, and the A-particle, suggesting that the epitopes on 2G8 are structurally conserved among the three capsid forms (Zhu R et al.
TextSentencer_T115 14692-14893 Sentence denotes 2G8 shows cross-reactivity against the CV-A10 procapsid, the mature virion, and the A-particle, suggesting that the epitopes on 2G8 are structurally conserved among the three capsid forms (Zhu R et al.
TextSentencer_T116 14894-14901 Sentence denotes 2018 ).
TextSentencer_T116 14894-14901 Sentence denotes 2018 ).
TextSentencer_T117 14902-15019 Sentence denotes The dynamic conformational changes occurring during the flavivirus life cycle have also been investigated by cryo-EM.
TextSentencer_T117 14902-15019 Sentence denotes The dynamic conformational changes occurring during the flavivirus life cycle have also been investigated by cryo-EM.
TextSentencer_T118 15020-15256 Sentence denotes Differing from the mature virus particles with smooth surfaces, immature virions appear as rough particles with 60 spikes comprising three E and three prM molecules (the pr peptide on top of each trimeric spike) (Perera and Kuhn 2008) .
TextSentencer_T118 15020-15256 Sentence denotes Differing from the mature virus particles with smooth surfaces, immature virions appear as rough particles with 60 spikes comprising three E and three prM molecules (the pr peptide on top of each trimeric spike) (Perera and Kuhn 2008) .
TextSentencer_T119 15257-15440 Sentence denotes As the pr peptide is cleaved during virus maturation and is absent in mature virions, anti-prM Fabs (e.g. 2H2 and 1H10) form complexes with immature DENV (Fig. 2K, 2N ) Wirawan et al.
TextSentencer_T119 15257-15440 Sentence denotes As the pr peptide is cleaved during virus maturation and is absent in mature virions, anti-prM Fabs (e.g. 2H2 and 1H10) form complexes with immature DENV (Fig. 2K, 2N ) Wirawan et al.
TextSentencer_T120 15441-15448 Sentence denotes 2019) .
TextSentencer_T120 15441-15448 Sentence denotes 2019) .
TextSentencer_T121 15449-15590 Sentence denotes Highly crossreactive E53, a fusion-loop-specific antibody, binds preferentially to spikes on immature DENV and WNV particles (Cherrier et al.
TextSentencer_T121 15449-15590 Sentence denotes Highly crossreactive E53, a fusion-loop-specific antibody, binds preferentially to spikes on immature DENV and WNV particles (Cherrier et al.
TextSentencer_T122 15591-15598 Sentence denotes 2009 ).
TextSentencer_T122 15591-15598 Sentence denotes 2009 ).
TextSentencer_T123 15599-15802 Sentence denotes Because these antibodies can trap flaviviruses in immature states, the neutralizing mechanism for them may depend on their capacity to block the normal transition occurring during the maturation process.
TextSentencer_T123 15599-15802 Sentence denotes Because these antibodies can trap flaviviruses in immature states, the neutralizing mechanism for them may depend on their capacity to block the normal transition occurring during the maturation process.
TextSentencer_T124 15803-16012 Sentence denotes Many cryo-EM studies have been performed to investigate antibody-virus particle interactions for different functional states, including the following ones: (1) Intermediate complexes during 'breathing' motion.
TextSentencer_T124 15803-16012 Sentence denotes Many cryo-EM studies have been performed to investigate antibody-virus particle interactions for different functional states, including the following ones: (1) Intermediate complexes during 'breathing' motion.
TextSentencer_T125 16013-16180 Sentence denotes Although each cryo-EM reconstruction usually represents a static snapshot of a specific conformation, structural plasticity in immune complexes can also be visualized.
TextSentencer_T125 16013-16180 Sentence denotes Although each cryo-EM reconstruction usually represents a static snapshot of a specific conformation, structural plasticity in immune complexes can also be visualized.
TextSentencer_T126 16181-16303 Sentence denotes Fab 1A1D-2 induces large conformation changes in the E protein and binds to normally partially hidden epitopes (Lok et al.
TextSentencer_T126 16181-16303 Sentence denotes Fab 1A1D-2 induces large conformation changes in the E protein and binds to normally partially hidden epitopes (Lok et al.
TextSentencer_T127 16304-16311 Sentence denotes 2008) .
TextSentencer_T127 16304-16311 Sentence denotes 2008) .
TextSentencer_T128 16312-16527 Sentence denotes Cryo-EM studies have also revealed that Fab 1A1D-2 only binds to epitopes near the fivefold and threefold vertices, suggesting that the extent of the breathing might be not evenly distributed over the viral surface.
TextSentencer_T128 16312-16527 Sentence denotes Cryo-EM studies have also revealed that Fab 1A1D-2 only binds to epitopes near the fivefold and threefold vertices, suggesting that the extent of the breathing might be not evenly distributed over the viral surface.
TextSentencer_T129 16528-16594 Sentence denotes (2) Size variations in the viral shells at different temperatures.
TextSentencer_T129 16528-16594 Sentence denotes (2) Size variations in the viral shells at different temperatures.
TextSentencer_T130 16595-16721 Sentence denotes It was found that when exposed to 37°C, DENV virions expand in size when compared with the structure at 4°C (Fibriansah et al.
TextSentencer_T130 16595-16721 Sentence denotes It was found that when exposed to 37°C, DENV virions expand in size when compared with the structure at 4°C (Fibriansah et al.
TextSentencer_T131 16722-16729 Sentence denotes 2013) .
TextSentencer_T131 16722-16729 Sentence denotes 2013) .
TextSentencer_T132 16730-17000 Sentence denotes The unexpanded virions at 4°C are covered by 180 copies of the 2D22 Fab (Fig. 2I, 2L) , whereas only 120 Fab copies are present on some expanded virions at 37°C (Fig. 2J, 2M) , as based on 2D and 3D classification of extracted virus-antibody particles (Fibriansah et al.
TextSentencer_T132 16730-17000 Sentence denotes The unexpanded virions at 4°C are covered by 180 copies of the 2D22 Fab (Fig. 2I, 2L) , whereas only 120 Fab copies are present on some expanded virions at 37°C (Fig. 2J, 2M) , as based on 2D and 3D classification of extracted virus-antibody particles (Fibriansah et al.
TextSentencer_T133 17001-17035 Sentence denotes 2015a) . (3) Fusion intermediates.
TextSentencer_T133 17001-17035 Sentence denotes 2015a) . (3) Fusion intermediates.
TextSentencer_T134 17036-17172 Sentence denotes A low pH-triggered rearrangement of the E protein is required for virus-cell membrane fusion during entry of flaviviruses into the cell.
TextSentencer_T134 17036-17172 Sentence denotes A low pH-triggered rearrangement of the E protein is required for virus-cell membrane fusion during entry of flaviviruses into the cell.
TextSentencer_T135 17173-17260 Sentence denotes The E16 Fab trapped WNV in a prefusion state when the virions were exposed to low pH ).
TextSentencer_T135 17173-17260 Sentence denotes The E16 Fab trapped WNV in a prefusion state when the virions were exposed to low pH ).
TextSentencer_T136 17261-17365 Sentence denotes C10, a bNAb for DENV, can structurally lock the E protein of ZIKV at acidic conditions (Rouvinski et al.
TextSentencer_T136 17261-17365 Sentence denotes C10, a bNAb for DENV, can structurally lock the E protein of ZIKV at acidic conditions (Rouvinski et al.
TextSentencer_T137 17366-17384 Sentence denotes 2015; Zhang et al.
TextSentencer_T137 17366-17384 Sentence denotes 2015; Zhang et al.
TextSentencer_T138 17385-17392 Sentence denotes 2016 ).
TextSentencer_T138 17385-17392 Sentence denotes 2016 ).
TextSentencer_T139 17393-17520 Sentence denotes Many severe human diseases are caused by structurally polymorphic enveloped viruses (e.g., HIV-1, influenza and Ebola viruses).
TextSentencer_T139 17393-17520 Sentence denotes Many severe human diseases are caused by structurally polymorphic enveloped viruses (e.g., HIV-1, influenza and Ebola viruses).
TextSentencer_T140 17521-17632 Sentence denotes Glycoprotein-specific antibody-inducing epitopes on the viral surface have been studied directly using cryo-ET.
TextSentencer_T140 17521-17632 Sentence denotes Glycoprotein-specific antibody-inducing epitopes on the viral surface have been studied directly using cryo-ET.
TextSentencer_T141 17633-17771 Sentence denotes The open conformations of the HIV-1 Env spike induced by Fab b12 or CD4/Fab 17b have been characterized using cryo-ET analysis (Liu et al.
TextSentencer_T141 17633-17771 Sentence denotes The open conformations of the HIV-1 Env spike induced by Fab b12 or CD4/Fab 17b have been characterized using cryo-ET analysis (Liu et al.
TextSentencer_T142 17772-17779 Sentence denotes 2008) .
TextSentencer_T142 17772-17779 Sentence denotes 2008) .
TextSentencer_T143 17780-18018 Sentence denotes The extent to which the C179 antibody bound to the stem domain of hemagglutinin (HA) on the influenza virus was also investigated by cryo-ET, revealing that most of the HA trimers on virions were accessible to this antibody (Harris et al.
TextSentencer_T143 17780-18018 Sentence denotes The extent to which the C179 antibody bound to the stem domain of hemagglutinin (HA) on the influenza virus was also investigated by cryo-ET, revealing that most of the HA trimers on virions were accessible to this antibody (Harris et al.
TextSentencer_T144 18019-18026 Sentence denotes 2013) .
TextSentencer_T144 18019-18026 Sentence denotes 2013) .
TextSentencer_T145 18027-18214 Sentence denotes High-resolution SPA of glycoprotein-antibody complexes requires stabilized protein samples, a good example of which is the engineered HIV-1 Env trimer with SOSIP mutations (Sanders et al.
TextSentencer_T145 18027-18214 Sentence denotes High-resolution SPA of glycoprotein-antibody complexes requires stabilized protein samples, a good example of which is the engineered HIV-1 Env trimer with SOSIP mutations (Sanders et al.
TextSentencer_T146 18215-18222 Sentence denotes 2002) .
TextSentencer_T146 18215-18222 Sentence denotes 2002) .
TextSentencer_T147 18223-18301 Sentence denotes Mature HIV-1 possesses trimers of gp41/gp120 homodimers as the surface spikes.
TextSentencer_T147 18223-18301 Sentence denotes Mature HIV-1 possesses trimers of gp41/gp120 homodimers as the surface spikes.
TextSentencer_T148 18302-18584 Sentence denotes Although some spike epitopes are present on the gp120 monomer, it would be desirable to choose native-like trimers for structural analysis because they are the major target of the neutralizing antibodies elicited by natural infection (Sanders and Moore 2017; Ward and Wilson 2017) .
TextSentencer_T148 18302-18584 Sentence denotes Although some spike epitopes are present on the gp120 monomer, it would be desirable to choose native-like trimers for structural analysis because they are the major target of the neutralizing antibodies elicited by natural infection (Sanders and Moore 2017; Ward and Wilson 2017) .
TextSentencer_T149 18585-18767 Sentence denotes SOSIP mutants contain an introduced disulfide (SOS) bond between the gp120 and gp41 ectodomains, and an introduced isoleucine to proline mutation in gp41 to promote trimer formation.
TextSentencer_T149 18585-18767 Sentence denotes SOSIP mutants contain an introduced disulfide (SOS) bond between the gp120 and gp41 ectodomains, and an introduced isoleucine to proline mutation in gp41 to promote trimer formation.
TextSentencer_T150 18768-19021 Sentence denotes Engineered glycoprotein trimers from other enveloped viruses (e.g., Middle East respiratory syndrome coronavirus, MERS-CoV, and parainfluenza virus types 1-4) were designed to present the antigenically optimal prefusion conformation Stewart-Jones et al.
TextSentencer_T150 18768-19021 Sentence denotes Engineered glycoprotein trimers from other enveloped viruses (e.g., Middle East respiratory syndrome coronavirus, MERS-CoV, and parainfluenza virus types 1-4) were designed to present the antigenically optimal prefusion conformation Stewart-Jones et al.
TextSentencer_T151 19022-19029 Sentence denotes 2018) .
TextSentencer_T151 19022-19029 Sentence denotes 2018) .
TextSentencer_T152 19030-19213 Sentence denotes Glycoproteins from Ebola virus were modified by removing the mucin-like domain, assembled as soluble trimers, and then studied in a complex with the ADI-15878 Fab by SPA (Murin et al.
TextSentencer_T152 19030-19213 Sentence denotes Glycoproteins from Ebola virus were modified by removing the mucin-like domain, assembled as soluble trimers, and then studied in a complex with the ADI-15878 Fab by SPA (Murin et al.
TextSentencer_T153 19214-19221 Sentence denotes 2018) .
TextSentencer_T153 19214-19221 Sentence denotes 2018) .
TextSentencer_T154 19222-19451 Sentence denotes Except for the above-mentioned trimeric forms, glycoprotein complexes containing more than one viral glycoprotein (e.g., gH/gL/gp42 from Epstein-Barr virus) have also been used for cryo-EM antibody-antigen studies (Snijder et al.
TextSentencer_T154 19222-19451 Sentence denotes Except for the above-mentioned trimeric forms, glycoprotein complexes containing more than one viral glycoprotein (e.g., gH/gL/gp42 from Epstein-Barr virus) have also been used for cryo-EM antibody-antigen studies (Snijder et al.
TextSentencer_T155 19452-19459 Sentence denotes 2018) .
TextSentencer_T155 19452-19459 Sentence denotes 2018) .
TextSentencer_T156 19460-19558 Sentence denotes Cryo-EM structures of glycoprotein-antibody complexes are usually captured in intermediate states.
TextSentencer_T156 19460-19558 Sentence denotes Cryo-EM structures of glycoprotein-antibody complexes are usually captured in intermediate states.
TextSentencer_T157 19559-19734 Sentence denotes Twenty antibody classes targeting six epitopes on the prefusion closed HIV-1 Env trimer have been characterized using SPA (Table 3) and crystallographic studies (Chuang et al.
TextSentencer_T157 19559-19734 Sentence denotes Twenty antibody classes targeting six epitopes on the prefusion closed HIV-1 Env trimer have been characterized using SPA (Table 3) and crystallographic studies (Chuang et al.
TextSentencer_T158 19735-19839 Sentence denotes 2019) . 'Breathing' by HIV-1 B41 SOSIP.664 trimers was found to expose the b12 epitope (Ozorowski et al.
TextSentencer_T158 19735-19839 Sentence denotes 2019) . 'Breathing' by HIV-1 B41 SOSIP.664 trimers was found to expose the b12 epitope (Ozorowski et al.
TextSentencer_T159 19840-19934 Sentence denotes 2017) , and a similar motion by influenza HA protomers was also revealed by SPA (Turner et al.
TextSentencer_T159 19840-19934 Sentence denotes 2017) , and a similar motion by influenza HA protomers was also revealed by SPA (Turner et al.
TextSentencer_T160 19935-19942 Sentence denotes 2019) .
TextSentencer_T160 19935-19942 Sentence denotes 2019) .
TextSentencer_T161 19943-20136 Sentence denotes S230 binding induces fusogenic conformational rearrangements in the SARS-CoV S glycoprotein, while the MERS-CoV S glycoprotein remains its prefusion conformation upon LCA60 binding Walls et al.
TextSentencer_T161 19943-20136 Sentence denotes S230 binding induces fusogenic conformational rearrangements in the SARS-CoV S glycoprotein, while the MERS-CoV S glycoprotein remains its prefusion conformation upon LCA60 binding Walls et al.
TextSentencer_T162 20137-20144 Sentence denotes 2019 ).
TextSentencer_T162 20137-20144 Sentence denotes 2019 ).
TextSentencer_T163 20145-20380 Sentence denotes VLPs with features that are structurally and immunologically indistinguishable from live viruses are used as alternative models for cryo-EM studies, especially when the viruses need to be manipulated in high-level biosafety facilities.
TextSentencer_T163 20145-20380 Sentence denotes VLPs with features that are structurally and immunologically indistinguishable from live viruses are used as alternative models for cryo-EM studies, especially when the viruses need to be manipulated in high-level biosafety facilities.
TextSentencer_T164 20381-20479 Sentence denotes Chikungunya virus (CHIKV) is a mosquitotransmitted human pathogen with T = 4 icosahedral symmetry.
TextSentencer_T164 20381-20479 Sentence denotes Chikungunya virus (CHIKV) is a mosquitotransmitted human pathogen with T = 4 icosahedral symmetry.
TextSentencer_T165 20480-20603 Sentence denotes On its surface, three E2 molecules form the major component of the viral spike and serve as the main target for antibodies.
TextSentencer_T165 20480-20603 Sentence denotes On its surface, three E2 molecules form the major component of the viral spike and serve as the main target for antibodies.
TextSentencer_T166 20604-20790 Sentence denotes Because handling live infectious CHIKV requires biosafety level 3 facilities, cryo-EM studies are performed with the safe CHIKV vaccine strain (CHIKV 181/25) or CHIK VLPs (Akahata et al.
TextSentencer_T166 20604-20790 Sentence denotes Because handling live infectious CHIKV requires biosafety level 3 facilities, cryo-EM studies are performed with the safe CHIKV vaccine strain (CHIKV 181/25) or CHIK VLPs (Akahata et al.
TextSentencer_T167 20791-20807 Sentence denotes 2010; Sun et al.
TextSentencer_T167 20791-20807 Sentence denotes 2010; Sun et al.
TextSentencer_T168 20808-20824 Sentence denotes 2013; Jin et al.
TextSentencer_T168 20808-20824 Sentence denotes 2013; Jin et al.
TextSentencer_T169 20825-20832 Sentence denotes 2015) .
TextSentencer_T169 20825-20832 Sentence denotes 2015) .
TextSentencer_T170 20833-21015 Sentence denotes The CHK-265 Fab cross-links two E2 molecules from neighboring spikes , while the footprints of C9 and IM-CKV063 Fabs on VLPs span the neighboring E2 subunits within one viral spike .
TextSentencer_T170 20833-21015 Sentence denotes The CHK-265 Fab cross-links two E2 molecules from neighboring spikes , while the footprints of C9 and IM-CKV063 Fabs on VLPs span the neighboring E2 subunits within one viral spike .
TextSentencer_T171 21016-21172 Sentence denotes CHK-152 may cross-link the flexible domain B to the domain A within an E2 molecule, and thus inhibiting the exposure of the fusion loop on domain II of E1 .
TextSentencer_T171 21016-21172 Sentence denotes CHK-152 may cross-link the flexible domain B to the domain A within an E2 molecule, and thus inhibiting the exposure of the fusion loop on domain II of E1 .
TextSentencer_T172 21173-21279 Sentence denotes VLPs have also served as controllable scaffolds for loading antigenic cargos (Charlton Hume and Lua 2017).
TextSentencer_T172 21173-21279 Sentence denotes VLPs have also served as controllable scaffolds for loading antigenic cargos (Charlton Hume and Lua 2017).
TextSentencer_T173 21280-21457 Sentence denotes Currently, the most commonly used VLPs are rigid icosahedral or helical particles, and flexible platforms are beginning to be promising roles for antigen loading (Hudalla et al.
TextSentencer_T173 21280-21457 Sentence denotes Currently, the most commonly used VLPs are rigid icosahedral or helical particles, and flexible platforms are beginning to be promising roles for antigen loading (Hudalla et al.
TextSentencer_T174 21458-21474 Sentence denotes 2014; Rao et al.
TextSentencer_T174 21458-21474 Sentence denotes 2014; Rao et al.
TextSentencer_T175 21475-21482 Sentence denotes 2018) .
TextSentencer_T175 21475-21482 Sentence denotes 2018) .
TextSentencer_T176 21483-21680 Sentence denotes To protect against different human papillomavirus (HPV, pseudo T = 7 icosahedral) infections, chimeric VLPs containing the epitopes from three HPV types have been generated and studied by cryo-EM .
TextSentencer_T176 21483-21680 Sentence denotes To protect against different human papillomavirus (HPV, pseudo T = 7 icosahedral) infections, chimeric VLPs containing the epitopes from three HPV types have been generated and studied by cryo-EM .
TextSentencer_T177 21681-21871 Sentence denotes Recently, computationally designed nanoparticles have also been examined by cryo-EM as a new platform for presenting the respiratory syncytial virus F glycoprotein trimer (Marcandalli et al.
TextSentencer_T177 21681-21871 Sentence denotes Recently, computationally designed nanoparticles have also been examined by cryo-EM as a new platform for presenting the respiratory syncytial virus F glycoprotein trimer (Marcandalli et al.
TextSentencer_T178 21872-21879 Sentence denotes 2019) .
TextSentencer_T178 21872-21879 Sentence denotes 2019) .
TextSentencer_T179 21880-22068 Sentence denotes Being able to add antigenic protein modules to tailorable platforms is a tantalizing way of studying highly virulent viruses like Crimean-Congo hemorrhagic fever, Nipah, and Ebola viruses.
TextSentencer_T179 21880-22068 Sentence denotes Being able to add antigenic protein modules to tailorable platforms is a tantalizing way of studying highly virulent viruses like Crimean-Congo hemorrhagic fever, Nipah, and Ebola viruses.
TextSentencer_T180 22069-22204 Sentence denotes It is also likely that the cryo-EM characterization of VLPs and nanoparticles will accelerate the development of new vaccine platforms.
TextSentencer_T180 22069-22204 Sentence denotes It is also likely that the cryo-EM characterization of VLPs and nanoparticles will accelerate the development of new vaccine platforms.
TextSentencer_T181 22205-22334 Sentence denotes Cryo-EM has evolved in recent years into a powerful technique for elucidating the structural basis of virusantibody interactions.
TextSentencer_T181 22205-22334 Sentence denotes Cryo-EM has evolved in recent years into a powerful technique for elucidating the structural basis of virusantibody interactions.
TextSentencer_T182 22335-22424 Sentence denotes Compared with traditional X-ray crystallography, cryo-EM offers the following advantages:
TextSentencer_T182 22335-22424 Sentence denotes Compared with traditional X-ray crystallography, cryo-EM offers the following advantages:
TextSentencer_T183 22425-22536 Sentence denotes (1) it can investigate conformational epitopes with sequentially discontinuous residues on icosahedral virions;
TextSentencer_T183 22425-22536 Sentence denotes (1) it can investigate conformational epitopes with sequentially discontinuous residues on icosahedral virions;
TextSentencer_T184 22537-22894 Sentence denotes (2) it avoids tedious screening for diffractable crystals and can be incorporated into a standardized process for rapid and rational vaccine development; (3) it can help with analyzing intrinsic heterogeneous samples, like highly glycosylated viral glycoproteins; and (4) it can be exploited for developing and characterizing high-quality vaccine platforms.
TextSentencer_T184 22537-22894 Sentence denotes (2) it avoids tedious screening for diffractable crystals and can be incorporated into a standardized process for rapid and rational vaccine development; (3) it can help with analyzing intrinsic heterogeneous samples, like highly glycosylated viral glycoproteins; and (4) it can be exploited for developing and characterizing high-quality vaccine platforms.
TextSentencer_T185 22895-23290 Sentence denotes Finally, cryo-EM studies of antigen-antibody complexes are beginning to clarify the mechanisms of epitope-paratope recognition at atomic resolution, so we expect that high-resolution cryo-EM structures will play more important roles in future at guiding vaccine development. and the ''One-Three-Five'' Strategic Programs of the Wuhan Institute of Virology, Chinese Academy of Sciences (Grant No.
TextSentencer_T185 22895-23290 Sentence denotes Finally, cryo-EM studies of antigen-antibody complexes are beginning to clarify the mechanisms of epitope-paratope recognition at atomic resolution, so we expect that high-resolution cryo-EM structures will play more important roles in future at guiding vaccine development. and the ''One-Three-Five'' Strategic Programs of the Wuhan Institute of Virology, Chinese Academy of Sciences (Grant No.
TextSentencer_T186 23291-23303 Sentence denotes Y605211SA3).
TextSentencer_T186 23291-23303 Sentence denotes Y605211SA3).
TextSentencer_T187 23304-23441 Sentence denotes We are thankful to the Center for Instrumental Analysis and Metrology of Wuhan Institute of Virology, CAS, for providing cryo-EM support.
TextSentencer_T187 23304-23441 Sentence denotes We are thankful to the Center for Instrumental Analysis and Metrology of Wuhan Institute of Virology, CAS, for providing cryo-EM support.
TextSentencer_T188 23442-23535 Sentence denotes We also thank Dr. Sandra Cheesman for editing the English text of a draft of this manuscript.
TextSentencer_T188 23442-23535 Sentence denotes We also thank Dr. Sandra Cheesman for editing the English text of a draft of this manuscript.
TextSentencer_T189 23536-23616 Sentence denotes Conflict of interest The authors declare that they have no conflict of interest.
TextSentencer_T189 23536-23616 Sentence denotes Conflict of interest The authors declare that they have no conflict of interest.
TextSentencer_T190 23617-23755 Sentence denotes Animal and Human Rights Statement This article does not contain any studies with human or animal subjects performed by any of the authors.
TextSentencer_T190 23617-23755 Sentence denotes Animal and Human Rights Statement This article does not contain any studies with human or animal subjects performed by any of the authors.
TextSentencer_T191 23756-24161 Sentence denotes Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creative commons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
TextSentencer_T191 23756-24161 Sentence denotes Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creative commons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.