Inhibition of host IRF3 by virus

IRF3 is a key transcriptional factor involved in the signaling pathway leading to establishment of antiviral state in infected cells. Under normal conditions, IRF3 exists in a latent form in the cytoplasm. Viral infection triggers the phosphorylation of IRF3 C-terminal region. The activated IRF3 migrates to the nucleus, where it complexes with the transcription coactivator CBP/p300, leading to the transcriptional activation of the IFN-alpha and IFN-beta genes.

RIGI RIGI STING TRIM25 MAVS TRADD TRADD TRAF3 TRAF6 TRAF2 FADD RIP1 TBK1 IKKe IRF3 IRF3 IRF7 IRF7 IKb IKb DDX3 IKKgamma IKKalpha IKKbeta NFKB NFKB NFKB

Due to its crucial role in innate response, IRF3 is the target of many viral proteins. Some viral proteins interact with IRF3 and prevent its phosphorylation such as SARS coronavirus PLpro protein, while others target IRF3 for proteasome-dependent degradation, like bICP0.