Effect of Cycloheximide on the Antiviral Action of Interferon

Abstract

Summary

Mouse embryo cultures treated with interferon in the presence of the inhibitor of protein synthesis, cycloheximide, showed substantially the same level of resistance as did the control cultures treated with interferon alone. In contrast fluorophenylalanine (FPA) prevented the development of resistance. When cells were treated for 5 hr with a combination of interferon, cycloheximide, and FPA, washed and then challenged with virus, antiviral resistance did develop. Mouse embryo cultures treated with a combination of interferon, cycloheximide and FPA to induce mRNA and then washed and refed with FPA-containing medium developed consistently less resistance than did cultures refed with medium alone. These findings were interpreted to indicate that in the presence of interferon and cycloheximide, mRNA for the antiviral protein (AVP) may be transcribed, and it is then rapidly translated after removal of cycloheximide. It also suggests that the hypothesized mRNA is unstable in the presence of FPA alone. Actinomycin D, added at the time of removal of interferon and cycloheximide did not prevent the development of antiviral resistance. This finding that the proposed mRNA for AVP is synthesized in the absence of protein synthesis and it is translated when production of additional RNA is inhibited by actinomycin D indicates that the formation of proposed AVP is directly induced by interferon without synthesis of newly induced, intermediary proteins. Taken together these findings support the working model that interferon exerts its antiviral activity by newly inducing an antiviral protein.