Synergistic Effects of HuIFN-γ on 2′,5′-Oligoadenylate Synthetase Induction by HuIFN-α

Abstract

Human skin fibroblast cells were treated with the three types of human interferon (HuIFN), α, β, and γ separately, and in series of combinations at different concentrations. The IFN-induced enzyme, 2′,5′-oligoadenylate (2-5A) synthetase, which is thought to be mediating the major part of the antiviral activity, was measured subsequent to 24 h treatment. The HuIFN-γ potentiated the induction of 2-5A synthetase elicited by either HuIFN-α or HuIFN-β, but the effect was seen only at low levels, i.e., 1–10 units. At higher levels, an antagonistic effect was seen. The individual subspecies of the HuIFN-α from native HuIFN-α were purified, separated, and analyzed for their ability to induce antiviral activity in human and bovine cells together with their capacity to induce 2-5A synthetase. Of the 12 species with molecular weights between 16,950 and 22,900 daltons, one species (MW 21,800) exerted peculiar properties in that it protected human cells better than bovine—at the same IFN level—and, it induced more 2-5A synthetase in human cells than in bovine cells.