Figure 1.

RIKA, a new anti-inflammatory function of IRF3. IRF3 is widely known for its transcriptional function involving the production of IFNβ and ISGs which antagonize various stages of viral replication. A non-transcriptional function of IRF3, RIPA (RIG-I-like receptor-induced IRF3 mediated Pathway of Apoptosis), was uncovered through our studies, involving IRF3 apoptotically killing virus-infected cells. In RIPA, linear ubiquitination of IRF3 upon virus infection results in its activation and translocation into the mitochondria. Subsequent activation of downstream caspases results in apoptotic cell death. RIKA, a new non-transcriptional function of IRF3, downregulates inflammatory gene expression. IRF3 domain, comprising 210–222 amino acids, interacts with the p65 subunit of NF-κB to sequester it in the cytosol. As a result, induction of inflammatory cytokines such as IL1β, Tnfα is restricted, thus suppressing the inflammatory responses and pathogenesis caused by the overproduction of these cytokines.