Ellis M N, Martin J L, Lobe D C, Johnsrude J D, Barry D W
J Antimicrob Chemother. 1986 Oct;18 Suppl B:95-101. doi: 10.1093/jac/18.supplement_b.95.
Induction of acyclovir resistance was studied in the immune compromised host by multiple passage of plaque-purified herpes simplex type I strains in athymic nude mice receiving suboptimal antiviral therapy. Mice infected with a highly pathogenic clinical isolate rapidly developed infections that were resistant to therapy. Viruses isolated from these mice had decreased in-vitro sensitivities to acyclovir, as well as altered characteristics when assayed by [125I]plaque autoradiography. In contrast, less virulent laboratory strains, or a genetically stable clinical isolate, showed no indication of mutation to resistance after extended passage in this mouse model. Highly pathogenic viruses may increase the probability of mutation to resistance because of the large amount of infectious virus they produce, while viruses of equivalent virulence may produce different amounts of drug-resistant progeny because of alterations in the replication fidelity of the viral DNA polymerase.
通过在接受次优抗病毒治疗的无胸腺裸鼠中对噬斑纯化的I型单纯疱疹病毒株进行多次传代，研究了免疫功能低下宿主中阿昔洛韦耐药性的诱导情况。感染高致病性临床分离株的小鼠迅速出现对治疗耐药的感染。从这些小鼠中分离出的病毒对阿昔洛韦的体外敏感性降低，并且在用[125I]噬斑放射自显影法检测时特性发生了改变。相比之下，毒力较低的实验室菌株或基因稳定的临床分离株，在该小鼠模型中经过长时间传代后未显示出耐药性突变的迹象。高致病性病毒可能因其产生的大量感染性病毒而增加耐药性突变的概率，而同等毒力的病毒可能由于病毒DNA聚合酶复制保真度的改变而产生不同数量的耐药后代。
