Vahlne A, Larsson P A, Horal P, Ahlmén J, Svennerholm B, Gronowitz J S, Olofsson S
Department of Clinical Virology, University of Göteborg, Sweden.
Arch Virol. 1992;122(1-2):61-75. doi: 10.1007/BF01321118.
Nontoxic concentrations of Cyclosporin A (CyA) dose-dependently inhibited herpes simplex virus (HSV) production in resting monkey kidney cells. The block was at the step of virus DNA synthesis as assessed by [3H]thymidine incorporation and by dot blot hybridization of infected cell DNA using a cloned 32P-labelled HSV DNA fragment (BamHI X) as probe. This was further supported by analysis of HSV protein synthesis in the presence of CyA as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. A relative accumulation of HSV alpha- (e.g., ICP 4) and beta 1-proteins (e.g., ICP 6 and 8) was found, whereas HSV gamma 1-proteins were slightly decreased and gamma 2-proteins were markedly decreased by CyA. The production of thymidine kinase and DNA polymerase was decreased when CyA was added to HSV infected cells. The sensitivity to CyA was not escaped by thymidine kinase nor DNA polymerase deficient mutants. Passage of HSV in presence of CyA did not result in induction of drug resistance.
无毒浓度的环孢素A（CyA）可剂量依赖性地抑制静息猴肾细胞中单纯疱疹病毒（HSV）的产生。通过[3H]胸苷掺入以及使用克隆的32P标记的HSV DNA片段（BamHI X）作为探针的感染细胞DNA斑点杂交评估，该阻断作用发生在病毒DNA合成步骤。十二烷基硫酸钠聚丙烯酰胺凝胶电泳和蛋白质免疫印迹分析评估了CyA存在下HSV蛋白质合成情况，进一步支持了这一结论。发现HSVα蛋白（如ICP 4）和β1蛋白（如ICP 6和8）相对积累，而CyA使HSVγ1蛋白略有减少，γ2蛋白显著减少。当将CyA添加到HSV感染细胞中时，胸苷激酶和DNA聚合酶的产生减少。胸苷激酶或DNA聚合酶缺陷型突变体对CyA不产生抗性。在CyA存在下传代HSV不会导致耐药性的诱导。
