INVOLVEMENT OF THE IRF FAMILY TRANSCRIPTION FACTOR IRF-3 IN VIRUS-INDUCED ACTIVATION OF THE IFN-BETA GENE

The virus-induced activation of interferon alpha/beta (IFN-alpha/beta) gene transcription is essential for host defense. The IFN-beta promot er is controlled primarily by the virus-inducible enhancer elements, t he IRF-Es. Here se show that IRF-3, an IRF family transcription factor , translocates to the nucleus from the cytoplasm upon virus infection in NIH/3T3 cells. The nuclear IRF-3 is phosphorylated, interacts with the co-activators CBP/p300, and binds specifically to the IFN-beta IRF -E. Furthermore, overexpression of IRF-3 causes a marked increase in v irus-induced IFN-beta mRNA expression, Thus, IRF-3 is a candidate tran scription factor mediating the activation of the IFN-beta gene. (C) 19 98 Federation of European Biochemical Societies.