Ida M, Kageyama S, Sato H, Kamiyama T, Yamamura J, Kurokawa M, Morohashi M, Shiraki K
Department of Virology, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Antiviral Res. 1999 Jan;40(3):155-66. doi: 10.1016/s0166-3542(98)00057-6.
We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fisher's exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.
我们通过比较耐药病毒出现的频率及其特征，在细胞培养中表征了阿昔洛韦和喷昔洛韦对水痘带状疱疹病毒（VZV）的不同作用。用无细胞病毒感染细胞，然后用浓度递增的阿昔洛韦或喷昔洛韦依次处理培养物。在存在6微克/毫升阿昔洛韦或喷昔洛韦的情况下选择耐药病毒。阿昔洛韦暴露后耐药病毒的出现频率显著高于喷昔洛韦暴露后（Fisher精确检验，P<0.0001），这可能反映了在这些实验条件下病毒生长的差异。基于抗病毒药物敏感性和胸苷激酶（TK）活性测定，在使用三种病毒株（川口株、Oka水痘疫苗株和一名带状疱疹患者的临床分离株）的七个实验中，发现11个阿昔洛韦耐药变体为TK缺陷型。对川口株TK缺陷变体的序列分析显示，缺失导致移码，从而导致TK基因过早终止。
