ABSTRACT
Interferons (IFNs) are among the first vertebrate immune pathways activated upon viral infection and are crucial for control of viral replication and dissemination, especially at mucosal surfaces as key locations for host exposure to pathogens. Inhibition of viral establishment and spread at and from these mucosal sites is paramount for preventing severe disease, while concomitantly limiting putative detrimental effects of inflammation. Here, we compare the roles of type I, II, and III IFNs in regulating three archetypal viruses - norovirus, herpes simplex virus, and severe acute respiratory virus coronavirus 2 (SARS-CoV-2) - which infect distinct mammalian mucosal tissues. Emerging paradigms include highly specific roles for IFNs in limiting local versus systemic infection, synergistic activities, and a spectrum of protective versus detrimental effects of IFNs during the infection response.