VESICULAR STOMATITIS-VIRUS INFECTION INDUCES A NUCLEAR DNA-BINDING FACTOR SPECIFIC FOR THE INTERFERON-STIMULATED RESPONSE ELEMENT

Vesicular stomatitis virus (VSV) has a broad host range. It replicates in the cytoplasm and causes rapid cytopathic effects. We show that fo llowing VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many ce ll types. This factor, tentatively called VSV-induced binding protein (VIBP), was estimated to have an approximate molecular mass of 50 kDa and was distinct from known members of the interferon regulatory facto r family, that are known to bind to the ISRE. Induction of VIBP requir ed tyrosine kinase activity but did not require cellular transcription . Treatment of cells with cycloheximide, which inhibits translation, o nly partially inhibited induction of VIBP. However, type I interferons and staurosporine, both of which inhibit VSV transcription, inhibited VIBP induction. Moreover, a double-stranded RNA analog, poly(I)-poly( C) also induced a DNA-binding activity very similar to that of VIBP. T hese results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral tr anscripts. The functional activity of VIBP was analyzed in cells stabl y transfected with a herpesvirus thymidine kinase-luciferase reporter gene that is under control of the ISRE. While activity of the control promoter without ISRE was strongly inhibited following VSV infection ( as a result of virus-mediated transcriptional shutdown of the host cel l), the inhibition was reversed by the ISRE-containing promoter, albei t partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other ce lls tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility.