Abstract
Replication of herpes simplex virus type 2 (HSV-2) was impeded in KB cells which were blocked in their capacity to synthesize DNA by 2 mM thymidine (TdR). The degree of inhibition was dependent upon the concentration of TdR. In marked contrast, HSV-1 is able to replicate under these conditions. The failure of HSV-2 to replicate is probably due to the inhibition of viral DNA synthesis; there was a marked reduction in the rate of DNA synthesis as well as the total amount of HSV-2 DNA made in the presence of 2 mM TdR. We postulated that the effect of TdR on viral replication occurs at the level of ribonucleotide reductase in a manner similar to KB cells. However, unlike KB cells, an altered ribonucleotide reductase activity, highly resistant to thymidine triphosphate inhibition, was found in extracts of HSV-2-infected KB cells. This activity was present in HSV-2-infected cells incubated in the presence or absence of TdR. Ribonucleotide reductase activity in extracts of HSV-1-infected KB cells showed a similar resistance to thymidine triphosphate inhibition. These results suggest that the effect of TdR on HSV-2 replication occurs at a stage of DNA synthesis other than reduction of cytidine nucleotides to deoxycytidine nucleotides.
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- Bjursell G., Reichard P. Effects of thymidine on deoxyribonucleoside triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. J Biol Chem. 1973 Jun 10;248(11):3904–3909. [PubMed] [Google Scholar]
- Cohen G. H. Ribonucleotide reductase activity of synchronized KB cells infected with herpes simplex virus. J Virol. 1972 Mar;9(3):408–418. doi: 10.1128/jvi.9.3.408-418.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen G. H., Vaughan R. K., Lawrence W. C. Deoxyribonucleic acid synthesis in synchronized mammalian KB cells infected with herpes simplex virus. J Virol. 1971 Jun;7(6):783–791. doi: 10.1128/jvi.7.6.783-791.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cooper G. M. Phosphorylation of 5-bromodeoxycytidine in cells infected with herpes simplex virus. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3788–3792. doi: 10.1073/pnas.70.12.3788. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan A. S. A brief review of the biochemistry of herpesvirus-host cell interaction. Cancer Res. 1973 Jun;33(6):1393–1398. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lawrence W. C. Evidence for a relationship between equine abortion (herpes) virus deoxyribonucleic acid synthesis and the S phase of the KB cell mitotic cycle. J Virol. 1971 Jun;7(6):736–748. doi: 10.1128/jvi.7.6.736-748.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ogino T., Shiman R., Rapp F. Deoxythymidine kinase from rabbit kidney cells infected with herpes simplex virus types 1 and 2. Intervirology. 1973;1(2):80–95. doi: 10.1159/000148835. [DOI] [PubMed] [Google Scholar]
- Pages J., Manteuil S., Stehelin D., Fiszman M., Marx M., Girard M. Relationship between replication of simian virus 40 DNA and specific events of the host cell cycle. J Virol. 1973 Jul;12(1):99–107. doi: 10.1128/jvi.12.1.99-107.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rapp F., Duff R. In vitro cell transformation by herpesviruses. Fed Proc. 1972 Nov-Dec;31(6):1660–1668. [PubMed] [Google Scholar]
- Setlow P. Deoxyribonucleic acid synthesis and deoxynucleotide metabolism during bacterial spore germination. J Bacteriol. 1973 Jun;114(3):1099–1107. doi: 10.1128/jb.114.3.1099-1107.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Skoog K. L., Nordenskjöld B. A., Bjursell K. G. Deoxyribonucleoside-triphosphate pools and DNA synthesis in synchronized hamster cells. Eur J Biochem. 1973 Mar 15;33(3):428–432. doi: 10.1111/j.1432-1033.1973.tb02699.x. [DOI] [PubMed] [Google Scholar]
- Studzinski G. P., Lambert W. C. Thymidine as a synchronizing agent. I. Nucleic acid and protein formation in synchronous HeLa cultures treated with excess thymidine. J Cell Physiol. 1969 Apr;73(2):109–117. doi: 10.1002/jcp.1040730204. [DOI] [PubMed] [Google Scholar]
- XEROS N. Deoxyriboside control and synchronization of mitosis. Nature. 1962 May 19;194:682–683. doi: 10.1038/194682a0. [DOI] [PubMed] [Google Scholar]