Abstract
Temperature-sensitive (ts) mutants in a number of complementation groups of herpes simplex virus type 1 (HSV-1) are deficient in DNA polymerase induction at the restrictive temperature. Twenty-two mutants in 15 complementation groups were tested for sensitivity to phosphonoacetate (PAA), a compound that inhibits HSV replication in vivo and the DNA polymerase in vitro. One mutant, tsD9, was resistant to PAA (Pr), whereas all others were sensitive. Revertants of tsD9 to the ts+ phenotype simultaneously lost PAA resistance. Additional Pr mutants were isolated from ts mutants belonging to several complementation groups of HSV-1. Double mutants (ts Pr phenotype) were used in three-factor recombination analyses to locate the PAA locus on the genetic map at a position indistinguishable from the ts lesion in tsD9. In all cases, resistance or sensitivity to PAA in vivo was correlated with resistance or sensitivity of DNA polymerase in vitro. These data are compatible with the temperature-sensitive lesion of tsD9 and the determinant of PAA sensitivity both residing in the structural gene for DNA polymerase.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aron G. M., Purifoy D. J., Schaffer P. A. DNA synthesis and DNA polymerase activity of herpes simplex virus type 1 temperature-sensitive mutants. J Virol. 1975 Sep;16(3):498–507. doi: 10.1128/jvi.16.3.498-507.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown S. M., Ritchie D. A., Subak-Sharpe J. H. Genetic studies with herpes simplex virus type 1. The isolation of temperature-sensitive mutants, their arrangement into complementation groups and recombination analysis leading to a linkage map. J Gen Virol. 1973 Mar;18(3):329–346. doi: 10.1099/0022-1317-18-3-329. [DOI] [PubMed] [Google Scholar]
- Courtney R. J., Schaffer P. A., Powell K. L. Synthesis of virus-specific polypaptides by temperature-sensitive mutants of herpes simplex virus type 1. Virology. 1976 Dec;75(2):306–318. doi: 10.1016/0042-6822(76)90030-1. [DOI] [PubMed] [Google Scholar]
- Esparza J., Purifoy D. J., Schaffer P. A., Benyesh-Melnick M. Isolation, complementation and preliminary phenotypic characterization of temperature-sensitive mutants of herpes simplex virus type 2. Virology. 1974 Feb;57(2):554–565. doi: 10.1016/0042-6822(74)90194-9. [DOI] [PubMed] [Google Scholar]
- Fried M., Griffin B. E. Organization of the genomes of polyoma virus and SV40. Adv Cancer Res. 1977;24:67–113. doi: 10.1016/s0065-230x(08)61013-1. [DOI] [PubMed] [Google Scholar]
- Hay J., Moss H., Jamieson A. T., Timbury M. C. Herpesvirus proteins: DNA polymerase and pyrimidine deoxynucleoside kinase activities in temperature-sensitive mutants of herpes simplex virus type 2. J Gen Virol. 1976 Apr;31(1):65–73. doi: 10.1099/0022-1317-31-1-65. [DOI] [PubMed] [Google Scholar]
- Hay J., Subak-Sharpe J. H. Mutants of herpes simplex virus types 1 and 2 that are resistant to phosphonoacetic acid induce altered DNA polymerase activities in infected cells. J Gen Virol. 1976 Apr;31(1):145–148. doi: 10.1099/0022-1317-31-1-145. [DOI] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Proteins specified by herpes simplex virus. XI. Identification and relative molar rates of synthesis of structural and nonstructural herpes virus polypeptides in the infected cell. J Virol. 1973 Dec;12(6):1347–1365. doi: 10.1128/jvi.12.6.1347-1365.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Keir H. M., Hay J., Morrison J. M., Subak-Sharpe H. Altered properties of deoxyribonucleic acid nucleotidyltransferase after infection of mammalian cells with herpes simplex virus. Nature. 1966 Apr 23;210(5034):369–371. doi: 10.1038/210369a0. [DOI] [PubMed] [Google Scholar]
- Mao J. C., Robishaw E. E. Mode of inhibition of herpes simplex virus DNA polymerase by phosphonoacetate. Biochemistry. 1975 Dec 16;14(25):5475–5479. doi: 10.1021/bi00696a015. [DOI] [PubMed] [Google Scholar]
- Mao J. C., Robishaw E. E., Overby L. R. Inhibition of DNA polymerase from herpes simplex virus-infected wi-38 cells by phosphonoacetic Acid. J Virol. 1975 May;15(5):1281–1283. doi: 10.1128/jvi.15.5.1281-1283.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Overby L. R., Robishaw E. E., Schleicher J. B., Rueter A., Shipkowitz N. L., Mao J. C. Inhibition of herpes simplex virus replication by phosphonoacetic acid. Antimicrob Agents Chemother. 1974 Sep;6(3):360–365. doi: 10.1128/aac.6.3.360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powell K. L., Courtney R. J. Polypeptide synthesized in herpes simplex virus type 2-infected HEp-2 cells. Virology. 1975 Jul;66(1):217–228. doi: 10.1016/0042-6822(75)90192-0. [DOI] [PubMed] [Google Scholar]
- Powell K. L., Purifoy D. J. Nonstructural proteins of herpes simplex virus. I. Purification of the induced DNA polymerase. J Virol. 1977 Nov;24(2):618–626. doi: 10.1128/jvi.24.2.618-626.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Purifoy D. J., Benyesh-Melnick M. DNA polymerase induction by DNA-negative temperature-sensitive mutants of herpes simplex virus type 2. Virology. 1975 Dec;68(2):374–386. doi: 10.1016/0042-6822(75)90280-9. [DOI] [PubMed] [Google Scholar]
- Purifoy D. J. Comparison of DNA polymerase activities induced by herpes simplex virus types 1 and 2. Intervirology. 1975;6(6):356–366. doi: 10.1159/000149492. [DOI] [PubMed] [Google Scholar]
- Schaffer P. A., Aron G. M., Biswal N., Benyesh-Melnick M. Temperature-sensitive mutants of herpes simplex virus type 1: isolation, complementation and partial characterization. Virology. 1973 Mar;52(1):57–71. doi: 10.1016/0042-6822(73)90398-x. [DOI] [PubMed] [Google Scholar]
- Schaffer P. A., Tevethia M. J., Benyesh-Melnick M. Recombination between temperature-sensitive mutants of herpes simplex virus type 1. Virology. 1974 Mar;58(1):219–228. doi: 10.1016/0042-6822(74)90156-1. [DOI] [PubMed] [Google Scholar]
- Schaffer P., Vonka V., Lewis R., Benyesh-Melnick M. Temperature-sensitive mutants of herpes simplex virus. Virology. 1970 Dec;42(4):1144–1146. doi: 10.1016/0042-6822(70)90364-8. [DOI] [PubMed] [Google Scholar]
- Shipkowitz N. L., Bower R. R., Appell R. N., Nordeen C. W., Overby L. R., Roderick W. R., Schleicher J. B., Von Esch A. M. Suppression of herpes simplex virus infection by phosphonoacetic acid. Appl Microbiol. 1973 Sep;26(3):264–267. doi: 10.1128/am.26.3.264-267.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Timbury M. C., Calder L. Temperature-sensitive mutants of herpes simplex virus type 2: a provisional linkage map based on recombination analysis. J Gen Virol. 1976 Feb;30(2):179–186. doi: 10.1099/0022-1317-30-2-179. [DOI] [PubMed] [Google Scholar]
- Watson D. H., Shedden W. I., Elliot A., Tetsuka T., Wildy P., Bourgaux-Ramoisy D., Gold E. Virus specific antigens in mammalian cells infected with herpes simplex virus. Immunology. 1966 Oct;11(4):399–408. [PMC free article] [PubMed] [Google Scholar]