The Antiviral Response to Gamma Interferon
Costa-Pereira, Ana P.
American Society for Microbiology
A role for alpha/beta interferon (IFN-α/β) in the IFN-γ antiviral response has long been suggested. Accordingly, possible roles for autocrine or double-stranded-RNA (dsRNA)-induced IFN-α/β in the IFN-γ response were investigated. Use was made of wild-type and a variety of mutant human fibrosarcoma cell lines, including mutant U5A cells, which lack a functional IFN-α/β receptor and hence an IFN-α/β response. IFN-γ did not induce detectable levels of IFN-α/β in any of the cell lines, nor was the IFN-γ response per se dependent on autocrine IFN-α/β. On the other hand, a number of responses to dsRNA [poly(I) · poly(C)] and encephalomyocarditis virus were greatly enhanced by IFN-γ pretreatment (priming) of wild-type cells or of mutant cells lacking an IFN-α/β response; these include the primary induction of dsRNA-inducible mRNAs, including IFN-β mRNA, and, to a lesser extent, the dsRNA-mediated activation of the p38 mitogen-activated protein (MAP) kinase(s). IFN-γ priming of mRNA induction by dsRNA is dependent on JAK1 and shows biphasic kinetics, with an initial rapid (