Fig. 1.

IFN sensing and signaling pathway. RNA viruses are internalized through several mechanisms, either fusion with the plasma membrane or binding to a surface receptor (ACE2 for SARS-CoV, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) for MHV). That internalization exposes the genomic RNA to the dsRNA sensing machinery in the cell; TLR3, RIGI and MDA5. These proteins signal the IRF-3 cascade leading to induction of IFNb and production of secreted IFNβ protein. That IFNβ protein can then bind IFNα/β receptors (INFAR1) on the surface of the same cell or surrounding cells. This activates the Stat1 signaling pathway to activate the many anti-viral genes found with ISRE promoter elements.