1887

Abstract

A recombinant of herpes simplex virus (HSV) was constructed in which the HSV thymidine kinase (TK) gene was deleted and the varicella-zoster virus (VZV) TK gene was introduced into the US5 region under the control of the human cytomegalovirus IE promoter. Infection with the recombinant (R18) led to the induction of TK although the kinetics of synthesis resembled those of a ‘late’ gene product. The recombinant was virulent in the zosteriform mouse model with the pattern of pathogenesis similar to that of wild-type HSV-1. The sensitivity of the recombinant to several nucleoside analogues was assessed and in most cases (BVaraU, ACV and GCV) it resembled VZV rather than HSV. The enhanced sensitivity of the recombinant to BVaraU compared with wild-type HSV resulted in a far greater response to treatment with BVaraU as assessed in the mouse model.

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1995-08-01
2024-04-20
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References

  1. Balan P., Davis-Poynter N., Bell S., Atkinson H., Browne H., Minson T. 1994; An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gl or the putative gJ. Journal of General Virology 75:1245–1258
    [Google Scholar]
  2. Bevilacqua F., Marcello A., Toni M., Zavattoni M., Cusini M., Zerboni R., Gerna G., Palu G. 1991; Acyclovir resistance/ susceptibility in herpes simplex vims type 2 sequential isolates from an AIDS patient. Journal of Acquired Immune Deficiency Syndrome 4:967–969
    [Google Scholar]
  3. Biron K. K., Elion G. B. 1980; In vitro susceptibility of varicella-zoster virus to acyclovir. Antimicrobial Agents and Chemotherapy 18:443–447
    [Google Scholar]
  4. Chen C., Okayama H. 1987; High-efficiency transformation of mammalian cells by plasmid DNA. Molecular and Cellular Biology 7:2745–2752
    [Google Scholar]
  5. Collins P., Appleyard G. A., Oliver N. M. 1982; Sensitivity of herpes simplex virus isolates from acyclovir clinical trials. American Journal of Medicine 73:380–382
    [Google Scholar]
  6. Darby G. 1993; The acyclovir legacy: its contribution to antiviral drug discovery. Journal of Medical Virology (Suppl.) 1:134–138
    [Google Scholar]
  7. Davison A. J., Scott J. E. 1986; The complete DNA sequence of varicella zoster virus. Journal of General Virology 67:1759–1816
    [Google Scholar]
  8. Dumas A. M., Geelen J. L. M. C., Weststrate M. W., Wertheim P., Van Der Noorda J. 1981; Xbal, Pstl, and Bgl II restriction enzyme maps of the two orientations of the varicella zoster genome. Journal of Virology 39:390–400
    [Google Scholar]
  9. Efstathiou S., Kemp S., Darby G., Minson A. C. 1989; The role of herpes simplex virus type 1 thymidine kinase in pathogenesis. Journal of General Virology 70:869–879
    [Google Scholar]
  10. Field A. K., Davis M. E., De Witt C., Perry H. C., Liou R., Germershausen J., Karkas J. D., Ashton W. T., Johnston D. B. R., Tolman R. L. 1983; 9-[2-hydroxy-1-(hydroxymethyl)-ethoxymethyl]guamne: a selective inhibitor of herpes group virus replication. Proceedings of the National Academy of Sciences, USA 80:4139–1143
    [Google Scholar]
  11. Forrester A., Farrell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T. 1992; Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. Journal of Virology 66:341–348
    [Google Scholar]
  12. Goodart S. A., Guzowsky J. F., Rice M. K., Wagner E. K. 1992; Effect of genomic location on expression of β-galactosidase mRNA controlled by the herpes simplex virus type 1 UL 38 promoter. Journal of Virology 66:2973–2981
    [Google Scholar]
  13. Haarr L., Marsden H. S., Preston C. M., Smiley J. R., Summers W. C., Summers W. P. 1985; Utilization of internal AUG codons for initiation of protein synthesis directed by mRNAs from normal and mutant genes encoding herpes simplex virus-specified thymidine kinase. Journal of Virology 56:512–519
    [Google Scholar]
  14. Hill T. J., Field H. J., Blyth W. A. 1975; Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. Journal of General Virology 28:341–353
    [Google Scholar]
  15. Jacobson J. G., Martin S. L., Coen D. M. 1989; A conserved open reading frame that overlaps the herpes simplex virus thymidine kinase gene is important for viral growth in cell culture. Journal of Virology 63:1839–1843
    [Google Scholar]
  16. Lacey S. F., Suzutani T., Powell K. L., Purifoy D. J. M., Honess R. W. 1991; Analysis of mutations in the thymidine kinase genes of drug-resistant varicella-zoster virus population using the polymerase chain reaction. Journal of General Virology 72:623–630
    [Google Scholar]
  17. McGeoch D. J., Dolan A., Donald S., Rixon F. J. 1985; Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. Journal of Molecular Biology 181:1–13
    [Google Scholar]
  18. Munyon W., Kraiselburd E., Davis S., Mann J. 1971; Transfer of thymidine kinase to thymidine kinaseless L-cells by infection with ultraviolet irradiated herpes simplex virus. Journal of Virology 7:813–820
    [Google Scholar]
  19. Myers M. G., Duer H. L., Hausler C. K. 1980; Experimental varicella-zoster virus infection of guinea pigs. Journal of Infectious Diseases 142:414–420
    [Google Scholar]
  20. Myers M. G., Connelly B. L., Stanberry L. R. 1991; Varicella in hairless guinea pigs. Journal of Infectious Diseases 163:746–751
    [Google Scholar]
  21. Purifoy D. J. M., Beauchamp L. M., de Miranda P., Ertl P., Lacey S., Roberts G., Rahim S. G., Darby G., Krenitsky T. A., Powell K. L. 1993; Review of research leading to new antiherpesvirus agents in clinical development: valaciclovir hydrochloride (256U, the L-valyl ester of acyclovir), and 882C, a specific agent for varicella-zoster virus. Journal of Medical Virology (Suppl.) 1:139–145
    [Google Scholar]
  22. Rahim S. G., Trevidi N., Selway J., Darby G., Collins P., Powell K. L., Purifoy D. J. M. 1992; 5-Alkynyl pyrimidine nucleosides as potent selective inhibitors of varicella-zoster virus. Antiviral Chemistry and Chemotherapy 3:293–297
    [Google Scholar]
  23. Roberts G. B., Fyfe J. A., McKee S. A., Rahim S. G., Daluge S. M., Almond M. R., Rideout J. L., Koszalka G. W., Krenitsky T. A. 1993; Varicella-zoster virus thymidine kinase: characterization and substrate specificity. Biochemical Pharmacology 46:2209–2218
    [Google Scholar]
  24. Roemer K., Johnson P. A., Friedmann T. 1991; Activity of the simian 40 early promoter-enhancer in herpes simplex virus type 1 vectors is dependent on its position, the infected cell type and the presence of Vmwl75. Journal of Virology 65:6900–6912
    [Google Scholar]
  25. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuch R., Horn G. T., Mullis K. B., Erlich H. A. 1988; Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239:487–488
    [Google Scholar]
  26. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, USA 74:5463–5467
    [Google Scholar]
  27. Simmons A., Nash A. A. 1984; Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. Journal of Virology 52:816–821
    [Google Scholar]
  28. Smee D. F., Martin J. C., Verheyden J. P. H., Matthews T. R. 1983; Anti-herpes activity of the acyclic nucleoside 9-(1, 3-di-hydroxy-2-propoxymethyl)guanine. Antimicrobial Agents and Chemotherapy 23:676–682
    [Google Scholar]
  29. Soike K., Huang J. L., Tu J. D., Stouffer B., Mitroka J. G., Swerdel M., Olsen S., Bonner D. P., Tuomari A. V., Fiel A. K. 1992; Oral bioavailability and anti-simian varicella virus efficacy of l-β-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) in monkeys. Journal of Infectious Diseases 165:732–736
    [Google Scholar]
  30. Speck P. G., Simmons A. 1991; Divergent molecular pathways of productive and latent infection with a virulent strain of herpes simplex virus type 1. Journal of Virology 65:4001–1005
    [Google Scholar]
  31. Summers W. P., Wagner M., Summers W. C. 1975; Possible peptide chain termination mutants in the thymidine kinase gene of a mammalian virus, herpes simplex virus. Proceedings of the National Academy of Sciences, USA 72:4081–4084
    [Google Scholar]
  32. Tenser R. B., Jones J. C., Ressel S. J., Fralish F. A. 1983; Thymidine plaque autoradiography of thymidine kinase-positive and thymidine kinase-negative herpesviruses. Journal of Clinical Microbiology 17:122–127
    [Google Scholar]
  33. Weber P. C., Levine M., Glorioso J. C. 1987; Rapid identification of nonessential genes of herpes simplex virus type 1 by Tn5 mutagenesis. Science 236:576–579
    [Google Scholar]
  34. Yokota T., Konno K., Mori S., Shigeta S., Kumagai M., Watanabe Y., Machida H. 1989; Mechanism of selective inhibition of varicella zoster virus replication by 1-β-D-arabino-furanosyl-E-5-(2-bromovinyl)uracil. Molecular Pharmacology 36:312–316
    [Google Scholar]
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