A large component of the antiviral activity of mouse interferon-gamma may be due to its induction of interferon-alpha.

The finding that interferon-gamma (IFN-gamma) may require two rounds of protein synthesis to induce the antiviral state raises the possibility that this IFN may not be directly antiviral. We, therefore, examined the possibility that IFN-gamma induces one or both of the other IFNs (alpha and/or beta) which in turn induce the antiviral state. Evidence is presented showing that under certain conditions a large portion of IFN-gamma's antiviral activity in mouse L-929 cells is mediated by its induction of IFN-alpha based on the findings that: 1) the antiviral activity of IFN-gamma in cells at low densities can be blocked by poly and monoclonal antibody to IFN-alpha and, 2) IFN-alpha can be demonstrated in the supernatant fluids of IFN-gamma treated cells. This report raises the possibility that a major antiviral mechanism of IFN-gamma is via induction of IFN-alpha in the mouse system. If the majority of the antiviral activity of IFN-gamma is via induction of other IFNs, then the role and mechanism of IFN-gamma might have to be reevaluated.