The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism

Wang, Yi; Liu, Li

Our initial study indicates that delivering the membrane gene into HEK293 cells markedly induces type I interferon (IFN-I) production (26) . To our knowledge, there are limited reports regarding the induction of IFN-␤ expression directly by viral structural genes. Therefore, it is intriguing to know which mechanism is responsible for the severe acute respiratory syndrome coronavirus (SARS-CoV) M gene-mediated IFN-␤ response. In this study, we demonstrate that SARS-CoV M protein, rather than its mRNA, activates IFN-␤ and NF-B responses through TLR-related TRAF3-independent signaling cascades. The driving force for M-mediated IFN-␤ induction was most likely generated from the inside of the cells. Using SARS-CoV pseudovirus as an infectious agent, we further show that single point mutation at the valine 68 residue of M protein markedly inhibits virus-induced IFN-␤ production. Overall, SARS-CoV M protein may stand out as a novel cytosolic PAMP in mediating the IFN-␤ immune response.