Induction of IRF-3/-7 kinase and NF-kappaB in response to double-stranded RNA and virus infection: common and unique pathways

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
T IwamuraT Fujita

Abstract

Infection by virus or treatment with double-stranded RNA (dsRNA) results in the activation of transcription factors including IRF-3, IRF-7 and a pleiotropic regulator NF-kappaB by specific phosphorylation. These factors are important in triggering a cascade of antiviral responses. A protein kinase that is yet to be identified is responsible for the activation of these factors and plays a key role in the responses. The signal cascade was analysed using sensitive assays for the activation of IRF-3 and NF-kappaB, and various inhibitors. We found that the activation of IRF-3 and NF-kappaB by dsRNA or virus involves a process that is sensitive to Geldanamycin. Although the induction of NF-kappaB by dsRNA/virus and TNF-alpha involves common downstream pathways including IKK activation, the upstream, Geldanamycin-sensitive process was unique to the dsRNA/virus-induced signal. By an in vitro assay using cell extract, we found an inducible protein kinase activity with physiological specificity of IRF-3 phosphorylation. Furthermore, the same extract specifically phosphorylated IRF-7 in a similar manner. Double-stranded RNA or virus triggers a specific signal cascade that results in the activation of the IRF-3/-7 kinase we detected, which...Continue Reading

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