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

If M protein indeed functions as a PAMP, blocking M protein synthesis should prevent the M-mediated activation of the IFN-␤ signaling pathway. Figure 5F clearly shows that M-stop reverses the M-mediated upregulation of the adaptor proteins MyD88 and TICAM2/TRAM in the initiating phase of TLR signaling pathways. Moreover, M-stop prevents the activation of the downstream modulator and key effectors of the IFN-␤ signaling pathway, such as TBK1, IRF3, and NF-B p65, in a dose-dependent manner (Fig. 5F ). Thus, blocking M protein translation could prevent M-mediated IFN-␤ induction by inactivating the TLRrelated signaling pathway.