The requirement of protein synthesis for VSV inhibition of host cell RNA synthesis.
Published ultraviolet (uv) inactivation data and in vitro transcription studies have suggested that vesicular stomatitis virus (VSV) leader RNA was solely responsible for the inhibition of host cell RNA synthesis by this virus. Since no protein product is encoded in leader RNA, this conclusion implied that no protein synthesis should be required for this effect. Therefore, the inhibitory activity of VSV was examined in the presence of the protein synthesis inhibitors, cycloheximide, pactamycin, and emetine. Protein synthesis inhibitors are known not to interfere with VSV primary transcription, but in their presence viral replication and amplification of transcription do not take place. Although at 39 degrees the VSV mutant tsG22 could undergo only primary transcription, maximum inhibition of host cell RNA synthesis took place. However, in the presence of the protein synthesis inhibitors the VSV mutant was no longer able to interfere with host cell RNA synthesis. These results could not be explained by a change in the concentration of intracellular leader RNA which remained unaltered by the drugs. Similar results were also obtained with wild-type VSV in the presence of cycloheximide. Upon removal of the drug, inhibition of host cell RNA synthesis was reestablished in parallel with the restoration of protein synthesis. It is concluded that protein synthesis is required for the inhibitory activity of VSV, presumably because the active inhibitory complex is a nucleoprotein containing leader RNA and either a cellular protein or the viral N protein. The cellular protein would have to be in limiting supply since de novo protein synthesis was required for the inhibition to take place.
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D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D009154:Mutation; D010142:Pactamycin / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012313:RNA / Q000235:genetics*; D012367:RNA, Viral / Q000302:isolation & purification; D012703:Serotyping; D014158:Transcription, Genetic / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics*; D014771:Virion / Q000235:genetics
D012367:RNA, Viral; D010142:Pactamycin; D012313:RNA; D003513:Cycloheximide; D004640:Emetine