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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.

IFN-alpha/beta has been suggested to require only one round of mRNA and protein synthesis to induce an antiviral state. We have examined the mechanism of induction of the antiviral states shown against three types of viruses: mengovirus (plus strand, sense RNA), vesicular stomatitis virus (VSV, minus strand RNA), and vaccinia virus (DNA). Mouse L cells were treated with IFN-alpha/beta and cycloheximide and then with actinomycin D on a schedule which allowed only one round of mRNA and protein synthesis. The cells were challenged with virus under single cycle growth conditions to determine the amount of antiviral activity against the particular challenge virus employed. These studies confirmed that most of the antiviral effect directed against VSV is achieved with one round of macromolecular synthesis. However, most of the antiviral effect directed against mengovirus and vaccinia virus seemed to require more than one round. These results suggest that IFN-alpha/beta induces two different antiviral states: one requiring one round of synthesis which is primarily responsible for the inhibition observed for VSV; and another requiring more than one round of synthesis which is primarily responsible for the inhibition observed for mengovirus and vaccinia virus.