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• W1551180964 startingPage "506" @default.
• W1551180964 abstract "Repeated passages of vaccinia virus in increasing concentrations of hydroxyurea followed by plaque purification resulted in the isolation of variants capable of growth in 5 mM hydroxyurea, a drug concentration which inhibited the reproduction of wild-type vaccinia virus 1,000-fold. Analyses of viral protein synthesis by using [35S]methionine pulse-labeling at intervals throughout the infection cycle revealed that all isolates overproduced a 34,000-molecular-weight (MW) early polypeptide. Measurement of ribonucleoside-diphosphate reductase (EC 1.17.4.1) activity after infection indicated that 4- to 10-fold more activity was induced by hydroxyurea-resistant viruses than by the wild-type virus. A two-step partial purification which yielded greater than 90% of the induced ribonucleotide reductase activity in the fraction obtained by 35% saturation with ammonium sulfate resulted in a substantial enrichment for the 34,000-MW protein from extracts of wild-type and hydroxyurea-resistant-virus-infected, but not mock-infected, cells. In the presence of the drug, the isolates incorporated [3H]thymidine into DNA earlier and at a rate substantially greater than that of the wild type, although the onset of DNA synthesis was delayed in both cases. In the absence of the drug, the attainment of a maximum viral DNA synthesis rate was accelerated after infection by drug-resistant isolates. The drug resistance trait was markedly unstable in all isolates. In the absence of selective pressure, plaque-purified isolates readily segregated progeny that displayed a wide range of resistance phenotypes. The results of this study indicate that vaccinia virus encodes a subunit of ribonucleotide reductase which is a 34,000-MW early protein whose overproduction confers hydroxyurea resistance on reproducing viruses." @default.
• W1551180964 created "2016-06-24" @default.
• W1551180964 creator A5028323895 @default.
• W1551180964 creator A5037113980 @default.
• W1551180964 date "1986-11-01" @default.
• W1551180964 modified "2023-09-29" @default.
• W1551180964 title "Hydroxyurea-resistant vaccinia virus: overproduction of ribonucleotide reductase" @default.
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• W1551180964 doi "https://doi.org/10.1128/jvi.60.2.506-514.1986" @default.
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