Cohen G H, Factor M N, Ponce de Leon M
J Virol. 1974 Jul;14(1):20-5. doi: 10.1128/JVI.14.1.20-25.1974.
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.
2毫摩尔胸腺嘧啶核苷（TdR）可抑制KB细胞合成DNA的能力，单纯疱疹病毒2型（HSV - 2）在这种细胞中的复制也受到阻碍。抑制程度取决于TdR的浓度。与之形成显著对比的是，HSV - 1在这些条件下能够复制。HSV - 2无法复制可能是由于病毒DNA合成受到抑制；在2毫摩尔TdR存在的情况下，DNA合成速率以及HSV - 2 DNA的总量均显著降低。我们推测，TdR对病毒复制的影响发生在核糖核苷酸还原酶水平，其作用方式与对KB细胞的影响类似。然而，与KB细胞不同的是，在感染HSV - 2的KB细胞提取物中发现了一种改变的核糖核苷酸还原酶活性，这种活性对三磷酸胸腺嘧啶核苷抑制具有高度抗性。无论是否存在TdR，这种活性都存在于感染HSV - 2的细胞中。感染HSV - 1的KB细胞提取物中的核糖核苷酸还原酶活性对三磷酸胸腺嘧啶核苷抑制也表现出类似的抗性。这些结果表明，TdR对HSV - 2复制的影响发生在DNA合成的一个阶段，而非胞嘧啶核苷酸还原为脱氧胞嘧啶核苷酸的阶段。
