Inhibition of vesicular stomatitis virus replication by frog virus 3: Selective action on secondary transcription

Abstract

We have investigated the mechanism by which heat-inactivated frog virus 3 (ΔFV 3) inhibits the replication of vesicular stomatitis virus (VSV). When added to cultures of baby hamster kidney cells, either before or within 1 hr of infection with VSV, ΔFV 3 inhibited the production of infectious VSV by 80–95%. If added after 1 hr, there was a precipitous drop in the inhibitory effect of the inactivated virus, suggesting that an early step in VSV replication was blocked. Analysis of [ 3H]uridine-labeled VSV RNA from cells exposed to ΔFV 3 at 1 hr before or 3 hr after VSV inoculation disclosed inhibition of both messenger and genome RNA synthesis. This reduction of total VSV RNA synthesis was found to result from an inhibition of secondary transcription and genome production by ΔFV 3: primary transcription was not affected. Inasmuch as ΔFV 3 also inhibited secondary transcription even when genome synthesis was blocked by cycloheximide, its effect on secondary transcription was not a consequence of decreased genome production. The sensitivity of the secondary transcribing complex of VSV to ΔFV 3 contrasts with the resistance of the complex involved in primary transcription. The ability of the inactivated frog virus to distinguish between these processes might be exploited as a probe of intracellular RNA synthesis by VSV.