Inhibition of herpes simplex virus type 2 replication by thymidine.
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.
D000596:Amino Acids; D000818:Animals; D002277:Carcinoma; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004279:DNA, Viral / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D007042:Hypoxanthines; D007668:Kidney; D009062:Mouth Neoplasms; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D012264:Ribonucleotide Reductases / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects* / Q000254:growth & development; D013936:Thymidine / Q000494:pharmacology*; D014316:Tritium; D014779:Virus Replication / Q000187:drug effects*
D000596:Amino Acids; D004279:DNA, Viral; D007042:Hypoxanthines; D014316:Tritium; D012313:RNA; D004247:DNA; D012264:Ribonucleotide Reductases; D013936:Thymidine