title: Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain.
abstract: Coronaviruses have developed various measures to evade innate immunity. We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM1) located at the N terminus. M protein from human coronavirus HKU1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM1 is capable of binding with RIG-I, TRAF3, TBK1 and IKKε, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M protein required for suppression of innate antiviral response.
authors: Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Kam-Leung
authors: KL
authors: Siu
authors: Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Chi-Ping
authors: CP
authors: Chan
authors: Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Kin-Hang
authors: KH
authors: Kok
authors: Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Patrick
authors: P
authors: Chiu-Yat Woo
authors: Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong.
authors: Dong-Yan
authors: DY
authors: Jin
mesh_terms: D017934:Coronavirus / Q000276:immunology*; D000086862:Coronavirus M Proteins; D006056:Golgi Apparatus / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D057131:Immune Evasion; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000821:virology; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000086862:Coronavirus M Proteins; D007370:Interferon Type I; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D048008:TNF Receptor-Associated Factor 3; D014763:Viral Matrix Proteins; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase