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 results may contradict some previous reports related to M-mediated IFN-I response. Siu et al. demonstrated that the M protein of SARS-CoV negatively regulated the dsRNA-induced and signaling molecule-induced IFN-I production. They also showed that M protein alone was unable to activate the IFN-I promoter activity (34) . One study even showed that M protein negatively regulates the NF-B signaling pathway (42) . A possible explanation for these discrepancies might be related to the M gene itself. Early study has shown that M protein possesses a higher substitution rate than other structural proteins in SARS-CoV, and the outcome of these substitutions alters the biochemical and immunological properties of M proteins (43, 44) . One amino acid alteration from valine to alanine at residue 68 is indeed found in the M protein from the GZ50 isolate studied by Siu et al. compared with the isolate used in the current study. Our functional analysis provides strong evidence to demonstrate that the valine-toalanine change at residue 68 of M protein is sufficient to abolish M-mediated IFN-␤ induction at both the transient-transfection level and the viral infection level (Fig. 1D and E and 8B and C) . Therefore, this amino acid substitution in M proteins indeed affects the interaction between M protein and the PRR for the subsequent IFN-I induction.