SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.
Identifieur interne : 001585 ( Main/Exploration ); précédent : 001584; suivant : 001586SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex.
Auteurs : Xiaojuan Chen [République populaire de Chine] ; Xingxing Yang ; Yang Zheng ; Yudong Yang ; Yaling Xing ; Zhongbin ChenSource :
- Protein & cell [ 1674-8018 ] ; 2014.
Descripteurs français
- KwdFr :
- Cellules HEK293, Dimérisation, Facteur-3 associé aux récepteurs de TNF (métabolisme), Facteur-3 de régulation d'interféron (métabolisme), Humains, I-kappa B Kinase (métabolisme), Interféron de type I (antagonistes et inhibiteurs), Interféron de type I (métabolisme), Liaison aux protéines, Papaïne (métabolisme), Peptide hydrolases (), Peptide hydrolases (métabolisme), Phosphorylation, Protein-Serine-Threonine Kinases (métabolisme), Protéines membranaires (), Protéines membranaires (génétique), Protéines membranaires (métabolisme), Structure tertiaire des protéines, Transduction du signal, Ubiquitinylation, Virus du SRAS (enzymologie).
- MESH :
- antagonistes et inhibiteurs : Interféron de type I.
- enzymologie : Virus du SRAS.
- génétique : Protéines membranaires.
- métabolisme : Facteur-3 associé aux récepteurs de TNF, Facteur-3 de régulation d'interféron, I-kappa B Kinase, Interféron de type I, Papaïne, Peptide hydrolases, Protein-Serine-Threonine Kinases, Protéines membranaires.
- Cellules HEK293, Dimérisation, Humains, Liaison aux protéines, Peptide hydrolases, Phosphorylation, Protéines membranaires, Structure tertiaire des protéines, Transduction du signal, Ubiquitinylation.
English descriptors
- KwdEn :
- Dimerization, HEK293 Cells, Humans, I-kappa B Kinase (metabolism), Interferon Regulatory Factor-3 (metabolism), Interferon Type I (antagonists & inhibitors), Interferon Type I (metabolism), Membrane Proteins (chemistry), Membrane Proteins (genetics), Membrane Proteins (metabolism), Papain (metabolism), Peptide Hydrolases (chemistry), Peptide Hydrolases (metabolism), Phosphorylation, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases (metabolism), SARS Virus (enzymology), Signal Transduction, TNF Receptor-Associated Factor 3 (metabolism), Ubiquitination.
- MESH :
- chemical , antagonists & inhibitors : Interferon Type I.
- chemical , chemistry : Membrane Proteins, Peptide Hydrolases.
- chemical , genetics : Membrane Proteins.
- chemical , metabolism : I-kappa B Kinase, Interferon Regulatory Factor-3, Interferon Type I, Membrane Proteins, Papain, Peptide Hydrolases, Protein-Serine-Threonine Kinases, TNF Receptor-Associated Factor 3.
- enzymology : SARS Virus.
- Dimerization, HEK293 Cells, Humans, Phosphorylation, Protein Binding, Protein Structure, Tertiary, Signal Transduction, Ubiquitination.
Abstract
SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.
DOI: 10.1007/s13238-014-0026-3
PubMed: 24622840
Affiliations:
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Le document en format XML
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dimerization</term>
<term>HEK293 Cells</term>
<term>Humans</term>
<term>I-kappa B Kinase (metabolism)</term>
<term>Interferon Regulatory Factor-3 (metabolism)</term>
<term>Interferon Type I (antagonists & inhibitors)</term>
<term>Interferon Type I (metabolism)</term>
<term>Membrane Proteins (chemistry)</term>
<term>Membrane Proteins (genetics)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Papain (metabolism)</term>
<term>Peptide Hydrolases (chemistry)</term>
<term>Peptide Hydrolases (metabolism)</term>
<term>Phosphorylation</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
<term>Protein-Serine-Threonine Kinases (metabolism)</term>
<term>SARS Virus (enzymology)</term>
<term>Signal Transduction</term>
<term>TNF Receptor-Associated Factor 3 (metabolism)</term>
<term>Ubiquitination</term>
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<term>Dimérisation</term>
<term>Facteur-3 associé aux récepteurs de TNF (métabolisme)</term>
<term>Facteur-3 de régulation d'interféron (métabolisme)</term>
<term>Humains</term>
<term>I-kappa B Kinase (métabolisme)</term>
<term>Interféron de type I (antagonistes et inhibiteurs)</term>
<term>Interféron de type I (métabolisme)</term>
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<term>Phosphorylation</term>
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<term>Protéines membranaires (génétique)</term>
<term>Protéines membranaires (métabolisme)</term>
<term>Structure tertiaire des protéines</term>
<term>Transduction du signal</term>
<term>Ubiquitinylation</term>
<term>Virus du SRAS (enzymologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Proteins</term>
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<term>Membrane Proteins</term>
<term>Papain</term>
<term>Peptide Hydrolases</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>TNF Receptor-Associated Factor 3</term>
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<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Interféron de type I</term>
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<term>Facteur-3 de régulation d'interféron</term>
<term>I-kappa B Kinase</term>
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<term>Peptide hydrolases</term>
<term>Protein-Serine-Threonine Kinases</term>
<term>Protéines membranaires</term>
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<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Peptide hydrolases</term>
<term>Phosphorylation</term>
<term>Protéines membranaires</term>
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<front><div type="abstract" xml:lang="en">SARS coronavirus (SARS-CoV) develops an antagonistic mechanism by which to evade the antiviral activities of interferon (IFN). Previous studies suggested that SARS-CoV papain-like protease (PLpro) inhibits activation of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism(s) used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro efficiently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain (PLpro-TM) from SARS-CoV inhibits STING/TBK1/IKKε-mediated activation of type I IFNs and disrupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBK1. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKKε, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activation of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is disrupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3-TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction with STING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity. </div>
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<name sortKey="Zheng, Yang" sort="Zheng, Yang" uniqKey="Zheng Y" first="Yang" last="Zheng">Yang Zheng</name>
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