Cargando…

Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex

Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this s...

Descripción completa

Detalles Bibliográficos
Autores principales: Siu, Kam-Leung, Kok, Kin-Hang, Ng, Ming-Him James, Poon, Vincent K. M., Yuen, Kwok-Yung, Zheng, Bo-Jian, Jin, Dong-Yan
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713514/
https://www.ncbi.nlm.nih.gov/pubmed/19380580
http://dx.doi.org/10.1074/jbc.M109.008227
_version_ 1782169585415356416
author Siu, Kam-Leung
Kok, Kin-Hang
Ng, Ming-Him James
Poon, Vincent K. M.
Yuen, Kwok-Yung
Zheng, Bo-Jian
Jin, Dong-Yan
author_facet Siu, Kam-Leung
Kok, Kin-Hang
Ng, Ming-Him James
Poon, Vincent K. M.
Yuen, Kwok-Yung
Zheng, Bo-Jian
Jin, Dong-Yan
author_sort Siu, Kam-Leung
collection PubMed
description Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons.
format Text
id pubmed-2713514
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-27135142010-06-12 Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex Siu, Kam-Leung Kok, Kin-Hang Ng, Ming-Him James Poon, Vincent K. M. Yuen, Kwok-Yung Zheng, Bo-Jian Jin, Dong-Yan J Biol Chem Mechanisms of Signal Transduction Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons. American Society for Biochemistry and Molecular Biology 2009-06-12 2009-04-20 /pmc/articles/PMC2713514/ /pubmed/19380580 http://dx.doi.org/10.1074/jbc.M109.008227 Text en © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.
spellingShingle Mechanisms of Signal Transduction
Siu, Kam-Leung
Kok, Kin-Hang
Ng, Ming-Him James
Poon, Vincent K. M.
Yuen, Kwok-Yung
Zheng, Bo-Jian
Jin, Dong-Yan
Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title_full Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title_fullStr Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title_full_unstemmed Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title_short Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex
title_sort severe acute respiratory syndrome coronavirus m protein inhibits type i interferon production by impeding the formation of traf3·tank·tbk1/ikkϵ complex
topic Mechanisms of Signal Transduction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713514/
https://www.ncbi.nlm.nih.gov/pubmed/19380580
http://dx.doi.org/10.1074/jbc.M109.008227
work_keys_str_mv AT siukamleung severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT kokkinhang severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT ngminghimjames severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT poonvincentkm severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT yuenkwokyung severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT zhengbojian severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex
AT jindongyan severeacuterespiratorysyndromecoronavirusmproteininhibitstypeiinterferonproductionbyimpedingtheformationoftraf3tanktbk1ikkecomplex