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

In addition to the TLR, which can be defined as a membraneassociated PRR, another set of PRRs is localized at the cytoplasm and mainly includes RIG-like receptors (RLRs) and NOD-like receptors (NLRs) to sense viral dsRNAs and bacterial cell wall components, respectively (2, 7) . The RLRs consist of at least three members, including RIG-I, MDA5, and LGP2. RIG-I recognizes 5=-triphosphate RNA and short dsRNA (4, 8) , while MDA5 senses long dsRNA (9) . An adaptor protein, MAVS, is required for the activation of the RIG-I/MDA5 signaling pathway. The association of viral nucleic acids with MAVS promotes the aggregation of MAVS on the mitochondrial membrane (10) . The "ligation" of TRAF3 with the aggregated MAVS may promote the phosphorylation of IRF3 that is required for IFN-␤ production (11) . A recent study also shows that an endoplasmic reticulum (ER)-derived adaptor protein, STING, could also function downstream of MAVS to promote IRF3 phosphorylation and the subsequent IFN-␤ response (12) .