1887

Abstract

SUMMARY

Mutants of HSV which are resistant to acyclovir (acycloguanosine) have been isolated following serial passages of several herpes simplex virus (HSV) strains in the presence of the drug. The majority of the mutants isolated are defective in induction of thymidine kinase (TK) and this is consistent with the observation that independently isolated TK viruses are naturally resistant to ACV. One mutant is described (SC16 RC) which is resistant in biochemically transformed cells which express HSV TK. This suggests that its resistance resides at a level other than TK. It is also resistant to phosphonoacetic acid, suggesting that the DNA polymerase locus may be involved. A further mutant is described [Cl (101) PC] which induces normal levels of TK, although the nature of resistance of this virus is not yet elucidated.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-49-1-115
1980-07-01
2022-01-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/49/1/JV0490010115.html?itemId=/content/journal/jgv/10.1099/0022-1317-49-1-115&mimeType=html&fmt=ahah

References

  1. Crumpacker C. S., ScHnipper L. E., Zaia J. A., Levin M. J. 1979; Growth inhibition by acycloguanosine of herpesviruses isolated from human infections. Antimicrobial Agents and Chemotherapy 15:642–645
    [Google Scholar]
  2. Darby G., Larder B. A., Bastow K. F., Field H. J. 1980; Sensitivity of viruses to phosphorylated 9-(2-hydroxyethoxymethyl)guanine revealed in TK-transformed cells. Journal of General Virology 49: (this part)
    [Google Scholar]
  3. Dubbs D. R., Kit S. 1964; Mutant strains of herpes simplex deficient in thymidine kinase-inducing activity. Virology 22:493–502
    [Google Scholar]
  4. Elion G. B., Furman P. A., Fyfe J. A., De miranda P., Beauchamp L., Schaeffer H. J. 1977; Selectivity of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proceedings of the National Academy of Sciences of the United States of America 74:5716–5720
    [Google Scholar]
  5. Field H. J., Darby G. 1980; The pathogenicity for mice of strains of herpes simplex virus which are resistant to Acyclovir in vitro and in vivo. Antimicrobial Agents and Chemotherapy 17: (in the press)
    [Google Scholar]
  6. Field H. J., Wildy P. 1978; The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. Journal of Hygiene, Cambridge 81:267–277
    [Google Scholar]
  7. Field H. J., Bell S. E., Elion G. B., Nash A. A., Wildy P. 1979; Effect of acycloguanosine treatment on acute and latent herpes simplex infections in mice. Antimicrobial Agents and Chemotherapy 15:554–561
    [Google Scholar]
  8. Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. 1978; Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. Journal of Biological Chemistry 253:8721–8727
    [Google Scholar]
  9. Hill T. J., Field H. I., 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]
  10. Honess R. W., Watson D. H. 1977; Herpes simplex virus resistance and sensitivity to phosphonoacetic acid. Journal of Virology 21:584–600
    [Google Scholar]
  11. Jamieson A. T., Gentry G. A., Subak-sharpe J. H. 1974; Induction of both thymidine and deoxycytidine kinase activity by herpes viruses. Journal of General Virology 24:465–480
    [Google Scholar]
  12. Kaufman H. E., Varnell E. D., Centifano Y. M., Rheinstrom S. D. 1978; Effect of 9-(2-hydroxyethoxy-methyl jguanine on herpesvirus-induced keratitis and iritis in rabbits. Antimicrobial Agents and Chemotherapy 14:842–845
    [Google Scholar]
  13. Klein R. J., Friedman-kien A. E., De stefano E. 1979; Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine. Antimicrobial Agents and Chemotherapy 15:723–729
    [Google Scholar]
  14. Klemperer H. G., Haynes G. R., Shedden W. I. H., Watson D. H. 1967; A virus-specific thymidine kinase in BHK21 cells infected with herpes simplex virus. Virology 31:120–128
    [Google Scholar]
  15. Minson A. C., Wildy P., Buchan A., Darby G. 1978; Introduction of the herpes simplex virus thymidine kinase gene into mouse cells using virus DNA or transformed cell DNA. Cell 13:581–587
    [Google Scholar]
  16. Park N.-H., Pavan-langston D., Mclean S. L., Albert D. M. 1979; Therapy of experimental herpes simplex encephalitis with aciclovir in mice. Antimicrobial Agents and Chemotherapy 15:775–779
    [Google Scholar]
  17. Summers W. P., Wagner M., Summers W. C. 1975; Possible peptide chain termination mutants in thymidine kinase gene of a mammalian virus, herpes simplex virus. Proceedings of the National Academy of Sciences of the United States of America 72:4081–4084
    [Google Scholar]
  18. Thouless M. E. 1972; Serological properties of thymidine kinase produced in cells infected with type 1 or type 2 herpes virus. Journal of General Virology 17:307–315
    [Google Scholar]
  19. Thouless M. E., Wildy P. 1975; Deoxypyrimidine kinases of herpes simplex viruses types 1 and 2: comparison of serological and structural properties. Journal of General Virology 26:159–170
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-49-1-115
Loading
/content/journal/jgv/10.1099/0022-1317-49-1-115
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error