DISTINCT ACTIVATION OF MURINE INTERFERON-ALPHA PROMOTER REGION BY IRF-1/ISFG-2 AND VIRUS-INFECTION

Virus infection in mouse L929 cells activates expression of interferon-alpha-4 (IFN-alpha-4), but not IFN-alpha-6. The integrity of a symmetrical sequence, GTAAAGAAA-GT (alpha-F1 site); (-103 to -93), present in the 35 nucleotide (nt) long inducible element (IE) (-109 to -75) of the alpha-4 promoter region is essential for the virus-induced expression. In the present study, we have shown that the interferon regulatory factor 1 (IRF-1) can induce expression of both IFN-alpha-4 and -alpha-6 in a transient expression assay. Virus infection cooperates with IRF-1 and further enhances transcription from the alpha-4 promoter, but inhibits the IRF-1-mediated expression from the alpha-6 promoter. The virus-mediated induction is determined by both IRF-1 and alpha-F1 sites, while activation by IRF-1 in a cotransfection assay is not greatly influenced by the alpha-F1 sequence. The activation of IFN-alpha gene promoters by IRF-1 was limited to the transient expression assay. The integrated alpha-4 promoter or the endogenous IFN-alpha genes could not be induced by transfection with IRF-1 expressing plasmid and IRF-1 did not up-regulate expression of the endogenous IRF-1 gene. However, expression of IRF-1 alone was sufficient to up-regulate the expression of two IFN stimulated genes, 2',5' oligoadenylate synthetase (OAS) and interferon stimulated (ISG)-15 gene. These results suggest that induction of IFN-alpha gene expression by virus infection requires cooperation between IRF-1 and another factor(s) that binds to the alpha-F1 sequence.