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: Kam-Leung Siu, Chi-Ping Chan, Kin-Hang Kok, Patrick Chiu-Yat Woo, Dong-Yan Jin
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 11 Issue 2 Pg. 141-9 (Mar 2014) ISSN: 2042-0226 [Electronic] China
• PMID: 24509444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Coronavirus M Proteins
• Interferon Type I
• Membrane Proteins
• Protein Sorting Signals
• TNF Receptor-Associated Factor 3
• Viral Matrix Proteins
• Protein Serine-Threonine Kinases
• TBK1 protein, human
• I-kappa B Kinase

Topics

• Coronavirus (immunology)
• Coronavirus M Proteins
• Golgi Apparatus (metabolism)
• HEK293 Cells
• HeLa Cells
• Humans
• I-kappa B Kinase (metabolism)
• Immune Evasion
• Immunity, Innate
• Immunosuppression Therapy
• Interferon Type I (metabolism)
• Membrane Proteins (genetics, metabolism)
• Mutation (genetics)
• Protein Binding (genetics)
• Protein Serine-Threonine Kinases (metabolism)
• Protein Sorting Signals (genetics)
• Protein Structure, Tertiary (genetics)
• Severe Acute Respiratory Syndrome (immunology, virology)
• TNF Receptor-Associated Factor 3 (metabolism)
• Viral Matrix Proteins (genetics, metabolism)