Field H, McMillan A, Darby G
J Infect Dis. 1981 Feb;143(2):281-5. doi: 10.1093/infdis/143.2.281.
Three acyclovir (ACV)-resistant mutants derived from a strain of herpes simplex virus (HSV) type 1 were studied to determine the range of their resistance to nine drugs active against HSV. Two of the mutants were thymidine kinase-deficient (TK-) and were resistant to drugs that are usually phosphorylated by HSV TK. The other mutant induced normal levels of TK; it was of special interest since TK+ viruses appear more likely to multiply well in vivo. This mutant was inhibited by "TK-mediated" drugs: idoxuridine, which is already in use, and two drugs with promising clinical potential, 1-beta-arabinofuranosylthymine and E-5-(2-bromovinyl)-2'-deoxyuridine. All of the mutants were sensitive to trifluorothymidine and 9-beta-D-arabinofuranosyladenine. These results suggest that the study of cross-resistance of HSV strains in vitro will aid in the investigation of alternative drugs for use in effective chemotherapy.
对从一株1型单纯疱疹病毒（HSV）衍生而来的三种阿昔洛韦（ACV）耐药突变体进行了研究，以确定它们对九种抗HSV活性药物的耐药范围。其中两个突变体缺乏胸苷激酶（TK-），对通常由HSV TK磷酸化的药物耐药。另一个突变体诱导出正常水平的TK；它特别令人感兴趣，因为TK+病毒似乎更有可能在体内良好增殖。这个突变体被“TK介导”的药物抑制：已在使用的碘苷，以及两种具有良好临床潜力的药物，1-β-阿拉伯呋喃糖基胸腺嘧啶和E-5-（2-溴乙烯基）-2'-脱氧尿苷。所有突变体对三氟胸苷和9-β-D-阿拉伯呋喃糖基腺嘌呤敏感。这些结果表明，体外研究HSV菌株的交叉耐药性将有助于研究用于有效化疗的替代药物。
