Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain.

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 IKK?, 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.
Mesh Terms:
Coronavirus, Golgi Apparatus, HEK293 Cells, HeLa Cells, Humans, I-kappa B Kinase, Immune Evasion, Immunity, Innate, Immunosuppression, Interferon Type I, Membrane Proteins, Mutation, Protein Binding, Protein Sorting Signals, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Severe Acute Respiratory Syndrome, TNF Receptor-Associated Factor 3, Viral Matrix Proteins
Cell. Mol. Immunol.
Date: Mar. 01, 2014
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