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. 1981 May;38(2):712–719. doi: 10.1128/jvi.38.2.712-719.1981

Gene expression of herpes simplex virus. III. Effect of arabinosyladenine on viral polypeptide synthesis.

M Pedersen, S Talley-Brown, R L Millette
PMCID: PMC171201  PMID: 6264138

Abstract

Arabinosyladenine, an established antiherpetic drug, was used to block herpes simplex virus type 1 DNA synthesis quantitatively in infected xeroderma pigmentosum cells. Kinetic analyses of viral polypeptides synthesized in the presence and absence of this drug revealed that there were at least six distinct kinetic classes of polypeptides. These differed in time of appearance after infection, time of maximum rate of synthesis, kinetics of turnoff, and sensitivity to arabinosyladenine. This study showed that arabinosyladenine had the following three main effects on herpes simplex virus type 1 gene expression. (i) The turnon of immediate early and delayed early polypeptides (kinetic classes 1 and 2) was retarded. (ii) The turnoff of early (immediate early and delayed early) polypeptides (classes 1 through 3) was delayed. (iii) The synthesis of late polypeptides (class 4 through 6) was inhibited by arabinosyladenine, with class 6 severely (80 to 90%) inhibited. The kinetic data presented here, along with the findings of other workers on the effects of inhibition of viral DNA synthesis, suggest that viral DNA replication is required for optimum synthesis of late viral polypeptides.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clements J. B., Watson R. J., Wilkie N. M. Temporal regulation of herpes simplex virus type 1 transcription: location of transcripts on the viral genome. Cell. 1977 Sep;12(1):275–285. doi: 10.1016/0092-8674(77)90205-7. [DOI] [PubMed] [Google Scholar]
  2. Cozzarelli N. R. The mechanism of action of inhibitors of DNA synthesis. Annu Rev Biochem. 1977;46:641–668. doi: 10.1146/annurev.bi.46.070177.003233. [DOI] [PubMed] [Google Scholar]
  3. Drach J. C., Shipman C., Jr The selective inhibition of viral DNA synthesis by chemotherapeutic agents: an indicator of clinical usefulness? Ann N Y Acad Sci. 1977 Mar 4;284:396–409. doi: 10.1111/j.1749-6632.1977.tb21976.x. [DOI] [PubMed] [Google Scholar]
  4. Ejercito P. M., Kieff E. D., Roizman B. Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol. 1968 May;2(3):357–364. doi: 10.1099/0022-1317-2-3-357. [DOI] [PubMed] [Google Scholar]
  5. Holland L. E., Anderson K. P., Shipman C., Jr, Wagner E. K. Viral DNA synthesis is required for the efficient expression of specific herpes simplex virus type 1 mRNA species. Virology. 1980 Feb;101(1):10–24. doi: 10.1016/0042-6822(80)90479-1. [DOI] [PubMed] [Google Scholar]
  6. Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Honess R. W., Watson D. H. Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. J Virol. 1977 Feb;21(2):584–600. doi: 10.1128/jvi.21.2.584-600.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jones P. C., Roizman B. Regulation of herpesvirus macromolecular synthesis. VIII. The transcription program consists of three phases during which both extent of transcription and accumulation of RNA in the cytoplasm are regulated. J Virol. 1979 Aug;31(2):299–314. doi: 10.1128/jvi.31.2.299-314.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Millette R. L., Klaiber R. Gene expression of herpes simplex virus. II. UV radiological analysis of viral transcription units. J Virol. 1980 Jun;34(3):604–614. doi: 10.1128/jvi.34.3.604-614.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Powell K. L., Purifoy D. J., Courtney R. J. The synthesis of herpes simplex virus proteins in the absence of virus DNA synthesis. Biochem Biophys Res Commun. 1975 Sep 2;66(1):262–271. doi: 10.1016/s0006-291x(75)80323-8. [DOI] [PubMed] [Google Scholar]
  11. Reinke C. M., Drach J. C., Shipman C., Jr, Weissbach A. Differential inhibition of mammalian DNA polymerases alpha, beta and gamma and herpes simplex virus-induced DNA polymerase by the 5'-triphosphates of arabinosyladenine and arabinosylcytosine. IARC Sci Publ. 1978;(24 Pt 2):999–1005. [PubMed] [Google Scholar]
  12. Roizman B. The herpesviruses--a biochemical definition of the group. Curr Top Microbiol Immunol. 1969;49:3–79. [PubMed] [Google Scholar]
  13. Schwartz P. M., Shipman C., Jr, Drach J. C. Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in the presence of an adenosine deaminase inhibitor. Antimicrob Agents Chemother. 1976 Jul;10(1):64–74. doi: 10.1128/aac.10.1.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shipman C., Jr, Smith S. H., Carlson R. H., Drach J. C. Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob Agents Chemother. 1976 Jan;9(1):120–127. doi: 10.1128/aac.9.1.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Swanstrom R. I., Pivo K., Wagner E. K. Restricted transcription of the herpes simplex virus genome occurring early after infection and in the presence of metabolic inhibitors. Virology. 1975 Jul;66(1):140–150. doi: 10.1016/0042-6822(75)90185-3. [DOI] [PubMed] [Google Scholar]
  16. Swanstrom R. I., Wagner E. K. Regulation of synthesis of herpes simplex type 1 virus mRNA during productive infection. Virology. 1974 Aug;60(2):522–533. doi: 10.1016/0042-6822(74)90346-8. [DOI] [PubMed] [Google Scholar]
  17. Talley-Brown S., Millette R. L. Gene expression of herpes simplex virus. I. Analysis of cytoplasmic RNAs in infected xeroderma pigmentosum cells. J Virol. 1979 Sep;31(3):733–740. doi: 10.1128/jvi.31.3.733-740.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ward R. L., Stevens J. G. Effect of cytosine arabinoside on viral-specific protein synthesis in cells infected with herpes simplex virus. J Virol. 1975 Jan;15(1):71–80. doi: 10.1128/jvi.15.1.71-80.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wolf H., Roizman B. The regulations of gamma (structural) polypeptide synthesis in herpes simplex virus types 1 and 2 infected cells. IARC Sci Publ. 1978;(24 Pt 1):327–336. [PubMed] [Google Scholar]

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