Identification of a Herpes Simplex Virus Type 1 Polypeptide Which Is a Component of the Virus-induced Ribonucleotide Reductase

Preston, Valerie G.; Palfreyman, John W.; Dutia, Bernadette M.

doi:10.1099/0022-1317-65-9-1457

Cited by 110 publications

(85 citation statements)

References 46 publications

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“…Our correlation data, of course, do not prove causality but the data are consistent with a causal relationship. Together with the observation that viral ribonucleotide reductase is needed for HSV-1 replication [15], we conclude that this enzyme is an important target for the development of antiviral drugs.…”

Section: Discussionsupporting

confidence: 61%

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

Turk

Shipman

Drach

1986

Biochemical Pharmacology

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Abstract-The effects of thiosemicarbazone derivatives of 2-acetylpyridine on mammalian and viral ribonucleoside diphosphate reductases were investigated. The enzymes were partially purified from uninfected and herpes simplex virus type-l (HSV-l)-infected KB cells by sequential salt fractionation with streptomycin sulfate and ammonium sulfate and by affinity chromatography on ATP-agarose. The five thiosemicarbazone derivatives investigated were all potent inhibitors of the virus-induced reductase. Fifty percent inhibitory concentrations (qO values) range from 2 to 13 PM. Four of the five derivatives also were inhibitors of the host cell reductase (1~~" values = 7-34 PM). A semicarbazone was inactive against the cellular enzyme and relatively weak as an inhibitor of the viral enzyme (ICY" = 340 PM). Four of the six compounds were preferential inhibitors of the viral reductase based on a comparison of ICY,, values (5 to >85-fold difference). Kinetic experiments revealed that inhibition of the HSV-1 reductase by the thiosemicarbazones was noncompetitive with respect to CDP and dithiothreitol. A comparison of the inhibitory effects of 2-acetylpyridine thiosemicarbazone itself on viral reductase and on virus replication in vitro demonstrated a similarity in the dose-response relationships for the two parameters. This observation supports the hypothesis that the HSV-induced ribonucleoside diphosphate reductase is an important target for the design of antiviral drugs.

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Section: Discussionsupporting

confidence: 61%

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

Turk

Shipman

Drach

1986

Biochemical Pharmacology

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“…4) makes a type 1 RR1, whereas its ~ mRNA stability is characteristic of the HSV-2 parent (G). Secondly, a temperature-sensitive mutant, ts1207 (Preston et al, 1984), with a mutation in the RR1 gene, makes stable ~ mRNA in the presence of CX at the non-permissive temperature. Others are unlikely candidates because they have probable functions already assigned (RR1, RR2) or are expressed late (gC).…”

Section: Discussionmentioning

confidence: 99%

On the Control of Immediate Early ( ) mRNA Survival in Cells Infected with Herpes Simplex Virus

Fenwick

Owen²

1988

Journal of General Virology

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SI~IMMARYThe ~ or immediate early mRNA of herpes simplex virus strain HSV-2(G) had a half-life of about 15 min if made in the absence of viral protein synthesis but was relatively stable if viral protein synthesis occurred, either freely or restricted by the presence of the proline analogue azetidine. In contrast, the ~ mRNA of other strains of the virus is stable, even in the absence of protein synthesis. Studies with recombinant viruses showed that the region of the viral DNA between 0.58 and 0.65 map units [which includes the gene (vhs, UL41) that controls virion-mediated shutoff of host protein synthesis] is important in determining the survival of ~ mRNA. In mixed infection experiments HSV-2(G) inhibited ~ as well as host protein synthesis but the shutoff activity appeared to be short-lived. Within 3 h after infection, as a result of protein synthesis, cells became completely resistant to shutoff by superinfecting virus.

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“…Included among these accessory genes are many of the nonessential glycoprotein genes and genes whose products contribute to viral DNA synthesis in nondividing cells, such as U L 23 encoding thymidine kinase 29 and U L 39/40 encoding ribonucleotide reductase. 30,31 Also included are genes which enhance the ability of the virus to prevent cellmediated interference with viral gene expression and protein synthesis (eg U L 41 encoding the virus host shutoff (vhs) function) [32][33][34] and genes that contribute to specialized aspects of the virus life cycle such as the establishment and maintenance of latency or reactivation from latency.…”

Section: Introductionmentioning

confidence: 99%

Development of herpes simplex virus replication-defective multigene vectors for combination gene therapy applications

et al. 1998

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Identification of a Herpes Simplex Virus Type 1 Polypeptide Which Is a Component of the Virus-induced Ribonucleotide Reductase

Cited by 110 publications

References 46 publications

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

On the Control of Immediate Early ( ) mRNA Survival in Cells Infected with Herpes Simplex Virus

Development of herpes simplex virus replication-defective multigene vectors for combination gene therapy applications

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