Deciphering the pathways to antiviral innate immunity and inflammation.

The antiviral innate immune and inflammatory responses are critical for host defense against viral infection. How these antiviral responses are initiated and regulated has been intensively investigated. Viral nucleic acids are sensed by pattern-recognition receptors (PRRs), which trigger various signaling pathways by utilizing distinct adaptor proteins, kinases and regulatory proteins. These pathways lead to activation of the transcriptional factors NF-κB and IRF3 and ultimate induction of antiviral effector proteins including type I interferons (IFNs), TNF and IL-1β, which are critical mediators of antiviral innate immune and inflammatory responses. For the past 20 years, our groups at Peking University and Wuhan University have made restless efforts in deciphering the molecular mechanisms of antiviral innate immune and inflammatory responses. Here, we summarize the major discoveries from our groups, including the identifications of the critical adaptors VISA/MAVS and MITA/STING, regulatory mechanisms of these adapter-mediated signaling, and regulation of TNF- and IL1β-triggered inflammatory responses.