IRF3 inhibits nuclear translocation of NF-κB to prevent viral inflammation

The innate immune response is the first line of defense against invading pathogens. Virus infection rapidly activates the intracellular signaling pathways, resulting in antiviral and inflammatory responses. The inflammatory response is beneficial for the early protection against the virus infection; however, unregulated inflammation is harmful to the host. We report a cellular antiinflammatory mechanism that inhibits the virus-induced inflammatory gene expression. Using cellular and mouse models, we reveal IRF3, a critical component of innate antiviral immunity, inhibits the activity of NF-κB, the pro-inflammatory transcription factor. Mechanistically, IRF3 binds the NF-κB-p65 subunit and prevents its translocation to the nucleus. It appears, therefore, that we have uncovered a previously unknown function for IRF3 in regulating viral inflammation.