PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway.
Identifieur interne : 001543 ( PubMed/Curation ); précédent : 001542; suivant : 001544PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway.
Auteurs : Gang Wang [République populaire de Chine] ; Gang Chen ; Dahai Zheng ; Genhong Cheng ; Hong TangSource :
- PloS one [ 1932-6203 ] ; 2011.
Descripteurs français
- KwdFr :
- Animaux, Cellules cultivées, Interféron de type I (métabolisme), Interféron de type I (physiologie), Maturation post-traductionnelle des protéines (génétique), Maturation post-traductionnelle des protéines (physiologie), Papaïne (), Papaïne (génétique), Papaïne (métabolisme), Protein-Serine-Threonine Kinases (antagonistes et inhibiteurs), Protein-Serine-Threonine Kinases (métabolisme), Protéines virales non structurales (), Protéines virales non structurales (génétique), Protéines virales non structurales (métabolisme), Protéines virales non structurales (physiologie), Souris, Structure tertiaire des protéines (génétique), Structure tertiaire des protéines (physiologie), Transduction du signal (génétique), Transduction du signal (physiologie), Transfection, Ubiquitinylation (génétique), Virus de l'hépatite murine (enzymologie), Virus de l'hépatite murine (métabolisme).
- MESH :
- antagonistes et inhibiteurs : Protein-Serine-Threonine Kinases.
- enzymologie : Virus de l'hépatite murine.
- génétique : Maturation post-traductionnelle des protéines, Papaïne, Protéines virales non structurales, Structure tertiaire des protéines, Transduction du signal, Ubiquitinylation.
- métabolisme : Interféron de type I, Papaïne, Protein-Serine-Threonine Kinases, Protéines virales non structurales, Virus de l'hépatite murine.
- physiologie : Interféron de type I, Maturation post-traductionnelle des protéines, Protéines virales non structurales, Structure tertiaire des protéines, Transduction du signal.
- Animaux, Cellules cultivées, Papaïne, Protéines virales non structurales, Souris, Transfection.
English descriptors
- KwdEn :
- Animals, Cells, Cultured, Interferon Type I (metabolism), Interferon Type I (physiology), Mice, Murine hepatitis virus (enzymology), Murine hepatitis virus (metabolism), Papain (chemistry), Papain (genetics), Papain (metabolism), Protein Processing, Post-Translational (genetics), Protein Processing, Post-Translational (physiology), Protein Structure, Tertiary (genetics), Protein Structure, Tertiary (physiology), Protein-Serine-Threonine Kinases (antagonists & inhibitors), Protein-Serine-Threonine Kinases (metabolism), Signal Transduction (genetics), Signal Transduction (physiology), Transfection, Ubiquitination (genetics), Viral Nonstructural Proteins (chemistry), Viral Nonstructural Proteins (genetics), Viral Nonstructural Proteins (metabolism), Viral Nonstructural Proteins (physiology).
- MESH :
- chemical , antagonists & inhibitors : Protein-Serine-Threonine Kinases.
- chemical , chemistry : Papain, Viral Nonstructural Proteins.
- chemical , genetics : Papain, Viral Nonstructural Proteins.
- chemical , metabolism : Interferon Type I, Papain, Protein-Serine-Threonine Kinases, Viral Nonstructural Proteins.
- chemical , physiology : Interferon Type I, Viral Nonstructural Proteins.
- enzymology : Murine hepatitis virus.
- genetics : Protein Processing, Post-Translational, Protein Structure, Tertiary, Signal Transduction, Ubiquitination.
- metabolism : Murine hepatitis virus.
- physiology : Protein Processing, Post-Translational, Protein Structure, Tertiary, Signal Transduction.
- Animals, Cells, Cultured, Mice, Transfection.
Abstract
Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response.
DOI: 10.1371/journal.pone.0017192
PubMed: 21364999
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pubmed:21364999Le document en format XML
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<front><div type="abstract" xml:lang="en">Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response.</div>
</front>
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<Month>09</Month>
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<ArticleTitle>PLP2 of mouse hepatitis virus A59 (MHV-A59) targets TBK1 to negatively regulate cellular type I interferon signaling pathway.</ArticleTitle>
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<Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus (SCoV) and mouse hepatitis virus A59 (MHV-A59) have evolved strategies to disable the innate immune system for productive replication and spread of infection. We have previously shown that papain-like protease domain 2 (PLP2), a catalytic domain of the nonstructural protein 3 (nsp3) of MHV-A59, encodes a deubiquitinase (DUB) and inactivates IFN regulatory factor 3 (IRF3) thereby the type I interferon (IFN) response.</AbstractText>
<AbstractText Label="PRINCIPAL FINDINGS" NlmCategory="RESULTS">Here we provide further evidence that PLP2 may also target TANK-binding kinase-1 (TBK1), the upstream kinase of IRF3 in the IFN signaling pathway. Overexpression experiments showed that PLP2 deubiquitinated TBK1 and reduced its kinase activity, hence inhibited IFN-β reporter activity. Albeit promiscuous in deubiquitinating cellular proteins, PLP2 inactivated TBK1 and IFN-β response in TNF receptor associated factor 3 (TRAF3) deficient cells, suggesting that targeting TBK1 would be sufficient for PLP2 to inhibit IRF3 activation. This notion was further supported by in vitro kinase assays, in which prior treatment of TBK1 with PLP2 inhibited its kinase activity to phosphorylate IRF3. Intriguing enough, results of PLP2 overexpression system and MHV-A59 infection system proved that PLP2 formed an inactive complex with TBK1 and IRF3 in the cytoplasm and the presence of PLP2 stabilized the hypo-phosphorylated IRF3-TBK1 complex in a dose-dependent manner.</AbstractText>
<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">These results suggest that PLP2 not only inactivates TBK1, but also prevents IRF3 nuclear translocation hence inhibits IFN transcription activation. Identification of the conserved DUB activity of PLP2 in suppression of IFN signaling would provide a useful clue to the development of therapeutics against coronaviruses infection.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Gang</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Chen</LastName>
<ForeName>Gang</ForeName>
<Initials>G</Initials>
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<Author ValidYN="Y"><LastName>Zheng</LastName>
<ForeName>Dahai</ForeName>
<Initials>D</Initials>
</Author>
<Author ValidYN="Y"><LastName>Cheng</LastName>
<ForeName>Genhong</ForeName>
<Initials>G</Initials>
</Author>
<Author ValidYN="Y"><LastName>Tang</LastName>
<ForeName>Hong</ForeName>
<Initials>H</Initials>
</Author>
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<Language>eng</Language>
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<Country>United States</Country>
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<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
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<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D017361">Viral Nonstructural Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C089383">nsP3 protein, virus</NameOfSubstance>
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<NameOfSubstance UI="C403191">TBK1 protein, human</NameOfSubstance>
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<NameOfSubstance UI="D010206">Papain</NameOfSubstance>
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<NameOfSubstance UI="C000657884">papain-like protease, Coronavirus</NameOfSubstance>
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