Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1986 Sep;30(3):502–504. doi: 10.1128/aac.30.3.502

Mutation within the herpes simplex virus DNA polymerase gene conferring resistance to (R)-9-(3,4-dihydroxybutyl)guanine.

H C Chiou, K M Kerns, D M Coen
PMCID: PMC180588  PMID: 3022642

Abstract

Five herpes simplex virus mutants known or presumed to contain mutations in their DNA polymerase genes conferring resistance to acyclovir and arabinosyladenine also proved to exhibit some degree of resistance to (R)-9-(3,4-dihydroxybutyl)guanine (buciclovir). For one mutant, a buciclovir resistance mutation was mapped to a region of the viral DNA polymerase gene proposed to encode the deoxynucleoside 5'-triphosphate binding domain. These data implicate the viral polymerase as a target of buciclovir action that contributes to its antiviral selectivity.

Full text

PDF
502

Selected References

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

  1. Chiou H. C., Weller S. K., Coen D. M. Mutations in the herpes simplex virus major DNA-binding protein gene leading to altered sensitivity to DNA polymerase inhibitors. Virology. 1985 Sep;145(2):213–226. doi: 10.1016/0042-6822(85)90155-2. [DOI] [PubMed] [Google Scholar]
  2. Coen D. M., Aschman D. P., Gelep P. T., Retondo M. J., Weller S. K., Schaffer P. A. Fine mapping and molecular cloning of mutations in the herpes simplex virus DNA polymerase locus. J Virol. 1984 Jan;49(1):236–247. doi: 10.1128/jvi.49.1.236-247.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Coen D. M., Fleming H. E., Jr, Leslie L. K., Retondo M. J. Sensitivity of arabinosyladenine-resistant mutants of herpes simplex virus to other antiviral drugs and mapping of drug hypersensitivity mutations to the DNA polymerase locus. J Virol. 1985 Feb;53(2):477–488. doi: 10.1128/jvi.53.2.477-488.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Coen D. M., Furman P. A., Aschman D. P., Schaffer P. A. Mutations in the herpes simplex virus DNA polymerase gene conferring hypersensitivity to aphidicolin. Nucleic Acids Res. 1983 Aug 11;11(15):5287–5297. doi: 10.1093/nar/11.15.5287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coen D. M., Furman P. A., Gelep P. T., Schaffer P. A. Mutations in the herpes simplex virus DNA polymerase gene can confer resistance to 9-beta-D-arabinofuranosyladenine. J Virol. 1982 Mar;41(3):909–918. doi: 10.1128/jvi.41.3.909-918.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crumpacker C. S., Schnipper L. E., Kowalsky P. N., Sherman D. M. Resistance of herpes simplex virus to adenine arabinoside and E-5-(2-bromovinyl)-2'-deoxyuridine: a physical analysis. J Infect Dis. 1982 Aug;146(2):167–172. doi: 10.1093/infdis/146.2.167. [DOI] [PubMed] [Google Scholar]
  7. Ericson A. C., Larsson A., Aoki F. Y., Yisak W. A., Johansson N. G., Oberg B., Datema R. Antiherpes effects and pharmacokinetic properties of 9-(4-hydroxybutyl) guanine and the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine. Antimicrob Agents Chemother. 1985 May;27(5):753–759. doi: 10.1128/aac.27.5.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fleming H. E., Jr, Coen D. M. Herpes simplex virus mutants resistant to arabinosyladenine in the presence of deoxycoformycin. Antimicrob Agents Chemother. 1984 Sep;26(3):382–387. doi: 10.1128/aac.26.3.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gibbs J. S., Chiou H. C., Hall J. D., Mount D. W., Retondo M. J., Weller S. K., Coen D. M. Sequence and mapping analyses of the herpes simplex virus DNA polymerase gene predict a C-terminal substrate binding domain. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7969–7973. doi: 10.1073/pnas.82.23.7969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Larsson A., Brännström G., Oberg B. Kinetic analysis in cell culture of the reversal of antiherpes activity of nucleoside analogs by thymidine. Antimicrob Agents Chemother. 1983 Nov;24(5):819–822. doi: 10.1128/aac.24.5.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Larsson A., Oberg B., Alenius S., Hagberg C. E., Johansson N. G., Lindborg B., Stening G. 9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication. Antimicrob Agents Chemother. 1983 May;23(5):664–670. doi: 10.1128/aac.23.5.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Larsson A., Sundqvist A., Parnerud A. M. Inhibition of herpes simplex virus-induced DNA polymerases and cellular DNA polymerase alpha by triphosphates of acyclic guanosine analogs. Mol Pharmacol. 1986 Jun;29(6):614–621. [PubMed] [Google Scholar]
  13. Larsson A., Tao P. Z. Phosphorylation of four acyclic guanosine analogs by herpes simplex virus type 2 thymidine kinase. Antimicrob Agents Chemother. 1984 Apr;25(4):524–526. doi: 10.1128/aac.25.4.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Smee D. F., Martin J. C., Verheyden J. P., Matthews T. R. Anti-herpesvirus activity of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine. Antimicrob Agents Chemother. 1983 May;23(5):676–682. doi: 10.1128/aac.23.5.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stenberg K., Larsson A., Datema R. Metabolism and mode of action of (R)-9-(3,4-dihydroxybutyl)guanine in herpes simplex virus-infected vero cells. J Biol Chem. 1986 Feb 15;261(5):2134–2139. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES