Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection.
Interferon (IFN)-stimulated gene factor 2 (ISGF2) plays a role in transcription of the beta IFN (IFN-beta) gene and IFN-stimulated genes (ISGs) and may function as a central mediator of cytokine responses. Constitutive ISGF2 transgene expression resulted in substantial resistance to three RNA virus families. This phenotype was not a consequence of IFN production and may have arisen directly through ISG expression. ISGF2 acted generally as a positive transcription factor through binding sites from several genes, in the context of transient cotransfection. Constitutive transcription of the endogenous IFN-beta gene, and several genes that are normally induced by either IFN-alpha or IFN-gamma, or only by IFN-alpha, was elevated in cells that constitutively express an ISGF2 transgene. However, constitutive and virus-induced levels of IFN-beta mRNA were unaffected in such cell lines.
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Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021-6399.
D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D004279:DNA, Viral; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014777:Virus Diseases / Q000276:immunology*; D014779:Virus Replication
D000914:Antibodies, Viral; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D014157:Transcription Factors; D007372:Interferons