Evidence that IFN-alph/beta induces two antiviral states active against different viruses

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.