Temperature-sensitive mutants in the vaccinia virus A18R gene increase double-stranded RNA synthesis as a result of aberrant viral transcription.

Abstract

Mutations in the vaccinia gene A18R cause activation of the cellular ribonucleolytic 2-5A pathway. To determine the mechanism of 2-5A pathway activation, mutant infections were analyzed for synthesis of double-stranded RNA and for transcription of individual virus genes. At late times postinfection, A18R mutant-infected cells contained an increased amount of complementary RNA and a higher steady state level of RNA from regions of the genome transcribed normally only early in the infection. The phenotype of A18R ts mutants is indistinguishable from that of wild-type infections done in the presence of isatin-beta-thiosemicarbazone (IBT). Actinomycin D is a potent inhibitor of activation of the 2-5A pathway in IBT-treated wt infections. Based on these observations, we conclude that the phenotype induced by A18R mutants or by IBT treatment of wt infections is caused by a loss of control of late viral transcription.

• Authors: C D Bayliss, R C Condit
• Journal: Virology (Virology) Vol. 194 Issue 1 Pg. 254-62 (May 1993) ISSN: 0042-6822 [Print] United States
• PMID: 8480421 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Double-Stranded
• RNA, Ribosomal
• RNA, Viral
• Dactinomycin
• isatin beta-thiosemicarbazone
• Isatin
• 2',5'-Oligoadenylate Synthetase
• Endoribonucleases
• 2-5A-dependent ribonuclease

Topics

• 2',5'-Oligoadenylate Synthetase (drug effects, metabolism)
• Dactinomycin (pharmacology)
• Endoribonucleases (metabolism)
• Enzyme Activation
• Gene Expression Regulation, Viral
• Genes, Viral (genetics)
• Isatin (analogs & derivatives, pharmacology)
• Mutation
• RNA, Double-Stranded (biosynthesis, drug effects)
• RNA, Ribosomal (metabolism)
• RNA, Viral (biosynthesis, drug effects)
• Transcription, Genetic
• Vaccinia virus (drug effects, genetics, growth & development)