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

Pathogen-associated molecular patterns (PAMPs) are pathogenborne components that can be sensed by either transmembrane, endolysosomal, or cytosolic sensors known as pattern recognition receptors (PRRs) (36) . In this study, we demonstrate that the membrane protein of SARS-CoV significantly upregulates IFN-␤ production by activating both NF-B and TBK1-IRF3 signaling cascades. Our data show that M-mediated IFN-␤ production is induced by M protein rather than M mRNA, indicating that pathogen-derived protein might be able to serve as a cytosolic PAMP. In addition, a mechanism study indicates that M proteinmediated IFN-␤ induction may be mainly due to the selective activation of TLR-related signaling pathways rather than the RLR signaling pathway in a TRAF3-independent manner. Overall, the current study indicates for the first time that pathogen-derived protein may function as a novel cytosolic PAMP to initiate a TLRrelated TRAF3-independent signaling pathway that subsequently promotes type I interferon (IFN-I) production.