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Article: Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3

TitleMiddle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3
Authors
Issue Date2016
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emi/marketing/index.html
Citation
Emerging Microbes & Infections, 2016, v. 5, article no. e39 How to Cite?
AbstractMiddle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.
Persistent Identifierhttp://hdl.handle.net/10722/234389
ISSN
2018 Impact Factor: 6.212
2015 SCImago Journal Rankings: 1.774
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLui, PY-
dc.contributor.authorWONG, LYR-
dc.contributor.authorFung, CL-
dc.contributor.authorSiu, KL-
dc.contributor.authorYeung, ML-
dc.contributor.authorYuen, KS-
dc.contributor.authorChan, CP-
dc.contributor.authorWoo, PCY-
dc.contributor.authorYuen, KY-
dc.contributor.authorJin, D-
dc.date.accessioned2016-10-14T13:46:31Z-
dc.date.available2016-10-14T13:46:31Z-
dc.date.issued2016-
dc.identifier.citationEmerging Microbes & Infections, 2016, v. 5, article no. e39-
dc.identifier.issn2222-1751-
dc.identifier.urihttp://hdl.handle.net/10722/234389-
dc.description.abstractMiddle East respiratory syndrome coronavirus (MERS-CoV) infection has claimed hundreds of lives and has become a global threat since its emergence in Saudi Arabia in 2012. The ability of MERS-CoV to evade the host innate antiviral response may contribute to its severe pathogenesis. Many MERS-CoV-encoded proteins were identified to have interferon (IFN)-antagonizing properties, which correlates well with the reduced IFN levels observed in infected patients and ex vivo models. In this study, we fully characterized the IFN-antagonizing property of the MERS-CoV M protein. Expression of MERS-CoV M protein suppressed type I IFN expression in response to Sendai virus infection or poly(I:C) induction. This suppressive effect was found to be specific for the activation of IFN regulatory factor 3 (IRF3) but not nuclear factor-κB. MERS-CoV M protein interacted with TRAF3 and disrupted TRAF3–TBK1 association leading to reduced IRF3 activation. M proteins from MERS-CoV and SARS-CoV have three highly similar conserved N-terminal transmembrane domains and a C-terminal region. Using chimeric and truncation mutants, the N-terminal transmembrane domains of the MERS-CoV M protein were found to be sufficient for its inhibitory effect on IFN expression, whereas the C-terminal domain was unable to induce this suppression. Collectively, our findings suggest a common and conserved mechanism through which highly pathogenic MERS-CoV and SARS-CoV harness their M proteins to suppress type I IFN expression at the level of TBK1-dependent phosphorylation and activation of IRF3 resulting in evasion of the host innate antiviral response.-
dc.languageeng-
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emi/marketing/index.html-
dc.relation.ispartofEmerging Microbes & Infections-
dc.titleMiddle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3-
dc.typeArticle-
dc.identifier.emailSiu, KL: sklsfx@hkucc.hku.hk-
dc.identifier.emailYeung, ML: pmlyeung@hku.hk-
dc.identifier.emailYuen, KS: samyuen@hku.hk-
dc.identifier.emailChan, CP: chancp10@hku.hk-
dc.identifier.emailWoo, PCY: pcywoo@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailJin, D: dyjin@hku.hk-
dc.identifier.authorityYeung, ML=rp01402-
dc.identifier.authorityChan, CP=rp02031-
dc.identifier.authorityWoo, PCY=rp00430-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityJin, D=rp00452-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/emi.2016.33-
dc.identifier.pmcidPMC4855074-
dc.identifier.scopuseid_2-s2.0-85003938202-
dc.identifier.hkuros267951-
dc.identifier.volume5-
dc.identifier.spagearticle no. e39-
dc.identifier.epagearticle no. e39-
dc.identifier.isiWOS:000375120900003-
dc.publisher.placeUnited Kingdom-
dc.identifier.f1000726445937-
dc.identifier.issnl2222-1751-

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