Regulation of interferon-induced antiviral states: contrasting profiles of decay in response to the removal of MuIFN-alpha, MuIFN-beta and MuIFN-gamma.

The stabilities of the antiviral states induced by different types of murine interferons (IFNs) were compared to gain insight into possible differences in the modes of regulation of their respective antiviral states. Both type I (MuIFN-alpha and MuIFN-beta) and type II (MuIFN-gamma) IFNs were employed to establish antiviral states against mengovirus in mouse L-929 cells. At various times after IFN treatment, the IFNs were removed and the stability of the antiviral states was determined by single cycle mengovirus yield reduction experiments. The antiviral states induced by the two type I IFNs decayed significantly by 12 h following IFN removal. The rate of this decay was an exponential function of the level of the antiviral state induced. A transcriptional block effectively delayed the decay of the antiviral state, suggesting the involvement of a positive feedback mechanism of regulation. In contrast, the profile of the antiviral state induced by type II IFN showed a significant enhancement upon MuIFN-gamma removal. This enhancement was not dependent upon de novo transcriptional and translational activity of the cells. These data suggest that the modes of regulation of the antiviral states against mengovirus induced by type I and type II IFNs are distinctly different.