Suzutani T, Machida H, Sakuma T
Department of Microbiology, Asahikawa Medical College, Japan.
Antimicrob Agents Chemother. 1988 Jul;32(7):1046-52. doi: 10.1128/AAC.32.7.1046.
Antiviral activities of five nucleoside analogs against the VR-3 and WT-34 strains of herpes simplex virus type 1 (HSV-1) were investigated in Vero and human embryo lung fibroblast (HEL) cells. In HEL cells, the compounds showed antiviral activities against both strains of HSV-1, but in Vero cells, the antiviral activities of the compounds were reduced in proportion to their antiviral indexes (the 50% inhibitory dose [ID50] for cell growth divided by the 50% plaque reduction dose for virus). The ratio of the ID50 in Vero cells to the ID50 in HEL cells was larger in VR-3-infected cells than in WT-34-infected cells. The following results were obtained. (i) Thymidine kinase (TK; EC 2.7.1.21) activity in the VR-3- or WT-34-infected Vero cells was about half that in VR-3- or WT-34-infected HEL cells. Induction of viral TK was especially low in the VR-3-infected Vero cells. (ii) The ID50 of the plaque reduction assay in hypoxanthine, aminopterin, and thymidine medium revealed that the activity of cellular thymidylate synthetase (EC 2.1.1.45) was important in viral replication in VR-3-infected Vero cells. (iii) The VR-3-infected cells required larger thymidine and thymidine phosphate pools for viral replication than the WT-34-infected cells did, although uptake of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil into infected cells was equal for both strains. (iv) In the VR-3-infected Vero cells, the quantity of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil triphosphate was smaller than that in VR-3-infected HEL cells and WT-34-infected Vero and HEL cells.
在非洲绿猴肾细胞（Vero细胞）和人胚肺成纤维细胞（HEL细胞）中研究了5种核苷类似物对1型单纯疱疹病毒（HSV-1）VR-3和WT-34毒株的抗病毒活性。在HEL细胞中，这些化合物对HSV-1的两种毒株均显示出抗病毒活性，但在Vero细胞中，化合物的抗病毒活性与其抗病毒指数（细胞生长的50%抑制剂量[ID50]除以病毒的50%蚀斑减少剂量）成比例降低。VR-3感染细胞中Vero细胞的ID50与HEL细胞中ID50的比值大于WT-34感染细胞。获得了以下结果。（i）VR-3或WT-34感染的Vero细胞中的胸苷激酶（TK；EC 2.7.1.21）活性约为VR-3或WT-34感染的HEL细胞中的一半。病毒TK的诱导在VR-3感染的Vero细胞中尤其低。（ii）在次黄嘌呤、氨基蝶呤和胸腺嘧啶核苷培养基中进行蚀斑减少试验的ID50表明，细胞胸苷酸合成酶（EC 2.1.1.45）的活性在VR-3感染的Vero细胞的病毒复制中很重要。（iii）VR-3感染的细胞比WT-34感染的细胞在病毒复制中需要更大的胸苷和磷酸胸苷池，尽管两种毒株感染细胞对1-β-D-阿拉伯呋喃糖基-E-5-(2-溴乙烯基)尿嘧啶的摄取量相等。（iv）在VR-3感染的Vero细胞中，1-β-D-阿拉伯呋喃糖基-E-5-(2-溴乙烯基)尿嘧啶三磷酸的量比VR-3感染的HEL细胞以及WT-34感染的Vero和HEL细胞中的量小。
