Disease relevance of IRF3

• Rotavirus non-structural protein NSP1 binds to and targets IRF3 for proteasome degradation early post-infection [1].
• Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro [2].
• Instead, the amino-terminal cysteine protease N(pro) of BVDV appears to be, at least partly, responsible for suppressing IRF-3 activation induced by Sendai virus infection [3].
• We conclude that the inhibition of IFN induction by this pestivirus involves a block to IRF-3 function, and we speculate that this may be a key characteristic for the survival of pestiviruses in nature [4].

High impact information on IRF3

• Cells infected with CSFV exhibited a lack of translocation of green fluorescent protein-IRF3 to the nucleus; however, constitutive shuttling of IRF3 was not blocked, since it could still accumulate in the nucleus in the presence of leptomycin B [2].
• Similar suppression of IRF-3-mediated responses was also observed with the Huh-7-BVDV replicon but was independent of NS3/4A protease activity [3].
• Induction of the IFN-beta promoter depends on the activation of three distinct transcription factors, NF-kappaB, ATF-2/c-Jun, and IFN regulatory factor 3 (IRF-3) [5].
• Mutational analysis of cysteine and histidine residues within the conserved N-terminal zinc-binding domain in NSP1 of bovine rotavirus strain B641 abolished IRF3 degradation in transfected cells [1].
• Non-cytopathogenic bovine viral diarrhoea virus (ncpBVDV) has previously been shown to inhibit the function of interferon regulatory factor-3 in cultured cells [J. Virol. 76 (2002) 8979] [6].

Biological context of IRF3

• Whereas NF-kappaB and ATF-2/c-Jun activities were readily detectable and comparable in both wt BRSV- and BRSV DeltaNS1/2-infected cells, phosphorylation and transcriptional activity of IRF-3, however, were observed only after BRSV DeltaNS1/2 infection [5].

Associations of IRF3 with chemical compounds

• The HCV replicon has been shown to block, via the NS3/4A serine protease, Sendai virus-induced activation of interferon regulatory factor 3 (IRF-3), a key antiviral signaling molecule [3].

References