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 following VSV infection, a nuclear factor that binds to a select set of interferon-stimulated responsive elements (ISRE) is induced in many cell 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 factor family, that are known to bind to the ISRE. Induction of VIBP required tyrosine kinase activity but did not require cellular transcription. Treatment of cells with cycloheximide, which inhibits translation, only 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. These results indicate that a preexisting cellular protein is activated upon VSV infection and that this activation requires primary viral transcripts. The functional activity of VIBP was analyzed in cells stably 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 cell), the inhibition was reversed by the ISRE-containing promoter, albeit partially, which suggests that VSV infection differentially affects transcription of host genes. Although VIBP was induced in all other cells tested, it was not induced in embryonal carcinoma cells after VSV infection, suggesting developmental regulation of VIBP inducibility.
Bovolenta
C
C
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
Lou
J
J
Kanno
Y
Y
Park
B K
BK
Thornton
A M
AM
Coligan
J E
JE
Schubert
M
M
Ozato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010750:Phosphoproteins / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D003609:Dactinomycin; D007372:Interferons; D003513:Cycloheximide; D011070:Poly I-C