Temperature-sensitive mutants in the vaccinia virus A18R gene increase double-stranded RNA synthesis as a result of aberrant viral transcription.
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.
Bayliss
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Department of Immunology and Medical Microbiology, University of Florida, Gainesville 32610.
Condit
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D015088:2',5'-Oligoadenylate Synthetase / Q000187:drug effects / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004722:Endoribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral / Q000235:genetics*; D007510:Isatin / Q000031:analogs & derivatives / Q000494:pharmacology; D009154:Mutation; D012330:RNA, Double-Stranded / Q000096:biosynthesis* / Q000187:drug effects; D012335:RNA, Ribosomal / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis* / Q000187:drug effects; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development
D012330:RNA, Double-Stranded; D012335:RNA, Ribosomal; D012367:RNA, Viral; D003609:Dactinomycin; C013578:isatin beta-thiosemicarbazone; D007510:Isatin; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease