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LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T211","span":{"begin":874,"end":877},"obj":"Body_part"},{"id":"T212","span":{"begin":909,"end":913},"obj":"Body_part"},{"id":"T213","span":{"begin":918,"end":923},"obj":"Body_part"},{"id":"T214","span":{"begin":2289,"end":2294},"obj":"Body_part"},{"id":"T215","span":{"begin":3134,"end":3142},"obj":"Body_part"},{"id":"T216","span":{"begin":3188,"end":3196},"obj":"Body_part"}],"attributes":[{"id":"A211","pred":"fma_id","subj":"T211","obj":"http://purl.org/sig/ont/fma/fma67095"},{"id":"A212","pred":"fma_id","subj":"T212","obj":"http://purl.org/sig/ont/fma/fma9664"},{"id":"A213","pred":"fma_id","subj":"T213","obj":"http://purl.org/sig/ont/fma/fma49184"},{"id":"A214","pred":"fma_id","subj":"T214","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A215","pred":"fma_id","subj":"T215","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A216","pred":"fma_id","subj":"T216","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"4.2.3. PLP2\nThe antiviral innate immune signaling pathways are regulated by several posttranslational modifications (PTMs), such as phosphorylation, ubiquitination, glycosylation, NEDDylation and SUMOylation [187], of which ubiquitination is a critical modification to modulate the stability and activity of PRRs and other components of innate immune signaling pathways. During viral infection, a reciprocatory action (occurrence of ubiquitination and deubiquitination) helps maintain the homeostasis of host immune responses. Hence, deubiquitinases (DUBs) are indispensable in the regulation of virus-induced type I IFN signaling [188]. Many host DUBs have been reported engaging in the regulation of innate immune signaling pathways [189,190,191]. In recent years, a variety of viral DUBs have been discovered to target key components of type I IFN pathway during various RNA virus infections. For example, foot-and-mouth disease virus leader proteinase (FMDV Lbpro) [192], and porcine reproductive and respiratory syndrome virus nsp2 (PRRSV nsp2) possess ubiquitin-deconjugating activity to deubiquitinate key host components [193,194]. To counteract host antiviral response, CoVs likely take advantage of DUB activity to break host innate immunity. Indeed, the PLPs of mouse hepatitis virus A59 (MHV-A59) [195], SARS [196], and human CoV NL63 have DUB activity and antagonize IFN induction [197]. PEDV PLP2 has been reported as having a deubiquitinase activity as well, and it can be co-immunoprecipitated by RIG-I and STING. As mentioned above, FMDV Lbpro, MHV PLP2 and SARS PLPs all counteract host innate immune response through blocking the ubiquitination of the components of RLRs pathways. Similarly, PEDV PLP2 removes the ubiquitinated conjugates from RIG-I and STING by its DUB activity, to negatively regulate type I IFN production. PEDV PLP2 probably interacts with RIG-I and STING, which prevents the activation of RIG-I and STING by hindering the recruitment of downstream signaling molecules. As expected, the interference with the ubiquitination of RIG-I and STING by PLP2 clearly benefits PEDV replication [80]. PEDV nsp3 contains two core domains of PLPs (PLPl and PLP2). It is determined that PEDV PLP2, but not PLP1, inhibits the IFN-β promoter activation in HEK293T cells. The DUB activity of PLP2 is highly dependent on its catalytic activity. Three catalytically inactive mutants of PEDV PLP2 (C1729A, H1888A and D1901A) are defective in the deubiquitination of its targets and fail to impair virus-induced IFN-β production.\nSARS-CoV PLP2 interacts with MDM2 (mouse double minute 2 homolog) to deubiquitinate and stabilize MDM2, approving the degradation of p53 and the suppression of IFN signaling [198]. PEDV infection degrades p53 by upregulation of MDM2 expression [198]. PEDV PLP2 may be responsible for targeting the p53 pathway and inhibiting p53-dependent apoptosis, leading to immune evasion. A recent study determined that TGEV PL1 inhibits the IFN-β expression and interferes with the RIG-1- and STING-mediated signaling pathway through a viral DUB activity [195]. It suggests that different viral proteins are involved in the deubiquitination of host proteins for different CoVs. However, these studies offer a probability to design a common therapeutic against different viral DUBs to reduce the replication and pathogenesis of CoVs. Therefore, further studies are required to understand more about the substrate specificity of these viral DUBs and clarify the precise functions of CoV protease/DUB activity."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T7","span":{"begin":909,"end":913},"obj":"Body_part"},{"id":"T8","span":{"begin":918,"end":923},"obj":"Body_part"}],"attributes":[{"id":"A7","pred":"uberon_id","subj":"T7","obj":"http://purl.obolibrary.org/obo/UBERON_0002387"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/UBERON_0000165"}],"text":"4.2.3. PLP2\nThe antiviral innate immune signaling pathways are regulated by several posttranslational modifications (PTMs), such as phosphorylation, ubiquitination, glycosylation, NEDDylation and SUMOylation [187], of which ubiquitination is a critical modification to modulate the stability and activity of PRRs and other components of innate immune signaling pathways. During viral infection, a reciprocatory action (occurrence of ubiquitination and deubiquitination) helps maintain the homeostasis of host immune responses. Hence, deubiquitinases (DUBs) are indispensable in the regulation of virus-induced type I IFN signaling [188]. Many host DUBs have been reported engaging in the regulation of innate immune signaling pathways [189,190,191]. In recent years, a variety of viral DUBs have been discovered to target key components of type I IFN pathway during various RNA virus infections. For example, foot-and-mouth disease virus leader proteinase (FMDV Lbpro) [192], and porcine reproductive and respiratory syndrome virus nsp2 (PRRSV nsp2) possess ubiquitin-deconjugating activity to deubiquitinate key host components [193,194]. To counteract host antiviral response, CoVs likely take advantage of DUB activity to break host innate immunity. Indeed, the PLPs of mouse hepatitis virus A59 (MHV-A59) [195], SARS [196], and human CoV NL63 have DUB activity and antagonize IFN induction [197]. PEDV PLP2 has been reported as having a deubiquitinase activity as well, and it can be co-immunoprecipitated by RIG-I and STING. As mentioned above, FMDV Lbpro, MHV PLP2 and SARS PLPs all counteract host innate immune response through blocking the ubiquitination of the components of RLRs pathways. Similarly, PEDV PLP2 removes the ubiquitinated conjugates from RIG-I and STING by its DUB activity, to negatively regulate type I IFN production. PEDV PLP2 probably interacts with RIG-I and STING, which prevents the activation of RIG-I and STING by hindering the recruitment of downstream signaling molecules. As expected, the interference with the ubiquitination of RIG-I and STING by PLP2 clearly benefits PEDV replication [80]. PEDV nsp3 contains two core domains of PLPs (PLPl and PLP2). It is determined that PEDV PLP2, but not PLP1, inhibits the IFN-β promoter activation in HEK293T cells. The DUB activity of PLP2 is highly dependent on its catalytic activity. Three catalytically inactive mutants of PEDV PLP2 (C1729A, H1888A and D1901A) are defective in the deubiquitination of its targets and fail to impair virus-induced IFN-β production.\nSARS-CoV PLP2 interacts with MDM2 (mouse double minute 2 homolog) to deubiquitinate and stabilize MDM2, approving the degradation of p53 and the suppression of IFN signaling [198]. PEDV infection degrades p53 by upregulation of MDM2 expression [198]. PEDV PLP2 may be responsible for targeting the p53 pathway and inhibiting p53-dependent apoptosis, leading to immune evasion. A recent study determined that TGEV PL1 inhibits the IFN-β expression and interferes with the RIG-1- and STING-mediated signaling pathway through a viral DUB activity [195]. It suggests that different viral proteins are involved in the deubiquitination of host proteins for different CoVs. However, these studies offer a probability to design a common therapeutic against different viral DUBs to reduce the replication and pathogenesis of CoVs. Therefore, further studies are required to understand more about the substrate specificity of these viral DUBs and clarify the precise functions of CoV protease/DUB activity."}

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T24","span":{"begin":1279,"end":1288},"obj":"Phenotype"}],"attributes":[{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0012115"}],"text":"4.2.3. PLP2\nThe antiviral innate immune signaling pathways are regulated by several posttranslational modifications (PTMs), such as phosphorylation, ubiquitination, glycosylation, NEDDylation and SUMOylation [187], of which ubiquitination is a critical modification to modulate the stability and activity of PRRs and other components of innate immune signaling pathways. During viral infection, a reciprocatory action (occurrence of ubiquitination and deubiquitination) helps maintain the homeostasis of host immune responses. Hence, deubiquitinases (DUBs) are indispensable in the regulation of virus-induced type I IFN signaling [188]. Many host DUBs have been reported engaging in the regulation of innate immune signaling pathways [189,190,191]. In recent years, a variety of viral DUBs have been discovered to target key components of type I IFN pathway during various RNA virus infections. For example, foot-and-mouth disease virus leader proteinase (FMDV Lbpro) [192], and porcine reproductive and respiratory syndrome virus nsp2 (PRRSV nsp2) possess ubiquitin-deconjugating activity to deubiquitinate key host components [193,194]. To counteract host antiviral response, CoVs likely take advantage of DUB activity to break host innate immunity. Indeed, the PLPs of mouse hepatitis virus A59 (MHV-A59) [195], SARS [196], and human CoV NL63 have DUB activity and antagonize IFN induction [197]. PEDV PLP2 has been reported as having a deubiquitinase activity as well, and it can be co-immunoprecipitated by RIG-I and STING. As mentioned above, FMDV Lbpro, MHV PLP2 and SARS PLPs all counteract host innate immune response through blocking the ubiquitination of the components of RLRs pathways. Similarly, PEDV PLP2 removes the ubiquitinated conjugates from RIG-I and STING by its DUB activity, to negatively regulate type I IFN production. PEDV PLP2 probably interacts with RIG-I and STING, which prevents the activation of RIG-I and STING by hindering the recruitment of downstream signaling molecules. As expected, the interference with the ubiquitination of RIG-I and STING by PLP2 clearly benefits PEDV replication [80]. PEDV nsp3 contains two core domains of PLPs (PLPl and PLP2). It is determined that PEDV PLP2, but not PLP1, inhibits the IFN-β promoter activation in HEK293T cells. The DUB activity of PLP2 is highly dependent on its catalytic activity. Three catalytically inactive mutants of PEDV PLP2 (C1729A, H1888A and D1901A) are defective in the deubiquitination of its targets and fail to impair virus-induced IFN-β production.\nSARS-CoV PLP2 interacts with MDM2 (mouse double minute 2 homolog) to deubiquitinate and stabilize MDM2, approving the degradation of p53 and the suppression of IFN signaling [198]. PEDV infection degrades p53 by upregulation of MDM2 expression [198]. PEDV PLP2 may be responsible for targeting the p53 pathway and inhibiting p53-dependent apoptosis, leading to immune evasion. A recent study determined that TGEV PL1 inhibits the IFN-β expression and interferes with the RIG-1- and STING-mediated signaling pathway through a viral DUB activity [195]. It suggests that different viral proteins are involved in the deubiquitination of host proteins for different CoVs. However, these studies offer a probability to design a common therapeutic against different viral DUBs to reduce the replication and pathogenesis of CoVs. Therefore, further studies are required to understand more about the substrate specificity of these viral DUBs and clarify the precise functions of CoV protease/DUB activity."}

LitCovid-PD-GO-BP

LitCovid-sentences

2_test

{"project":"2_test","denotations":[{"id":"32403318-28885059-82827428","span":{"begin":209,"end":212},"obj":"28885059"},{"id":"32403318-27012466-82827429","span":{"begin":632,"end":635},"obj":"27012466"},{"id":"32403318-21119682-82827430","span":{"begin":736,"end":739},"obj":"21119682"},{"id":"32403318-25070846-82827431","span":{"begin":740,"end":743},"obj":"25070846"},{"id":"32403318-25972356-82827432","span":{"begin":744,"end":747},"obj":"25972356"},{"id":"32403318-21307201-82827433","span":{"begin":970,"end":973},"obj":"21307201"},{"id":"32403318-22072774-82827434","span":{"begin":1130,"end":1133},"obj":"22072774"},{"id":"32403318-20504922-82827435","span":{"begin":1134,"end":1137},"obj":"20504922"},{"id":"32403318-18957937-82827436","span":{"begin":1310,"end":1313},"obj":"18957937"},{"id":"32403318-24622840-82827437","span":{"begin":1322,"end":1325},"obj":"24622840"},{"id":"32403318-16104827-82827438","span":{"begin":1395,"end":1398},"obj":"16104827"},{"id":"32403318-23596270-82827439","span":{"begin":2126,"end":2128},"obj":"23596270"},{"id":"32403318-25505178-82827440","span":{"begin":2725,"end":2728},"obj":"25505178"},{"id":"32403318-25505178-82827441","span":{"begin":2795,"end":2798},"obj":"25505178"},{"id":"32403318-18957937-82827442","span":{"begin":3095,"end":3098},"obj":"18957937"}],"text":"4.2.3. PLP2\nThe antiviral innate immune signaling pathways are regulated by several posttranslational modifications (PTMs), such as phosphorylation, ubiquitination, glycosylation, NEDDylation and SUMOylation [187], of which ubiquitination is a critical modification to modulate the stability and activity of PRRs and other components of innate immune signaling pathways. During viral infection, a reciprocatory action (occurrence of ubiquitination and deubiquitination) helps maintain the homeostasis of host immune responses. Hence, deubiquitinases (DUBs) are indispensable in the regulation of virus-induced type I IFN signaling [188]. Many host DUBs have been reported engaging in the regulation of innate immune signaling pathways [189,190,191]. In recent years, a variety of viral DUBs have been discovered to target key components of type I IFN pathway during various RNA virus infections. For example, foot-and-mouth disease virus leader proteinase (FMDV Lbpro) [192], and porcine reproductive and respiratory syndrome virus nsp2 (PRRSV nsp2) possess ubiquitin-deconjugating activity to deubiquitinate key host components [193,194]. To counteract host antiviral response, CoVs likely take advantage of DUB activity to break host innate immunity. Indeed, the PLPs of mouse hepatitis virus A59 (MHV-A59) [195], SARS [196], and human CoV NL63 have DUB activity and antagonize IFN induction [197]. PEDV PLP2 has been reported as having a deubiquitinase activity as well, and it can be co-immunoprecipitated by RIG-I and STING. As mentioned above, FMDV Lbpro, MHV PLP2 and SARS PLPs all counteract host innate immune response through blocking the ubiquitination of the components of RLRs pathways. Similarly, PEDV PLP2 removes the ubiquitinated conjugates from RIG-I and STING by its DUB activity, to negatively regulate type I IFN production. PEDV PLP2 probably interacts with RIG-I and STING, which prevents the activation of RIG-I and STING by hindering the recruitment of downstream signaling molecules. As expected, the interference with the ubiquitination of RIG-I and STING by PLP2 clearly benefits PEDV replication [80]. PEDV nsp3 contains two core domains of PLPs (PLPl and PLP2). It is determined that PEDV PLP2, but not PLP1, inhibits the IFN-β promoter activation in HEK293T cells. The DUB activity of PLP2 is highly dependent on its catalytic activity. Three catalytically inactive mutants of PEDV PLP2 (C1729A, H1888A and D1901A) are defective in the deubiquitination of its targets and fail to impair virus-induced IFN-β production.\nSARS-CoV PLP2 interacts with MDM2 (mouse double minute 2 homolog) to deubiquitinate and stabilize MDM2, approving the degradation of p53 and the suppression of IFN signaling [198]. PEDV infection degrades p53 by upregulation of MDM2 expression [198]. PEDV PLP2 may be responsible for targeting the p53 pathway and inhibiting p53-dependent apoptosis, leading to immune evasion. A recent study determined that TGEV PL1 inhibits the IFN-β expression and interferes with the RIG-1- and STING-mediated signaling pathway through a viral DUB activity [195]. It suggests that different viral proteins are involved in the deubiquitination of host proteins for different CoVs. However, these studies offer a probability to design a common therapeutic against different viral DUBs to reduce the replication and pathogenesis of CoVs. Therefore, further studies are required to understand more about the substrate specificity of these viral DUBs and clarify the precise functions of CoV protease/DUB activity."}

LitCovid-PubTator

PMC:7281546 / 34136-37682 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7281546 / 34136-37682 JSON TXT