Sibrack C D, McLaren C, Barry D W
Am J Med. 1982 Jul 20;73(1A):372-5. doi: 10.1016/0002-9343(82)90125-5.
Herpes simplex virus (HSV) type 1 from a bone marrow transplant recipient and HSV type 2 from a patient with genital herpes infection were examined for sensitivity to acyclovir after both patients received therapy with the drug. A 38- and 83-fold shift in sensitivity was detected in association with a marked decrease in viral thymidine kinase activity in isolates from both patients. The resistant HSV-1 isolate was approximately 900 times less neurovirulent to Balb/C mice but had similar cutaneous virulence in hairless mice compared with the patient's sensitive strain. In contrast, there was no difference in pathogenicity between the sensitive and resistant HSV-2 isolates. Latency was detected in the trigeminal ganglia of mice after snout inoculation with both the sensitive and resistant HSV-1 isolates. The ganglion isolate from the resistant HSV-inoculated mouse was found to be sensitive to acyclovir, implying a selection for or reversion of the sensitive phenotype. No trigeminal ganglion latency was detected after inoculation with either HSV-2 isolate. Resistance to acyclovir can arise during therapy as a result of diminished viral thymidine kinase activity but does not appear to be associated with increased virulence.
对一名骨髓移植受者的1型单纯疱疹病毒（HSV）和一名生殖器疱疹感染患者的2型单纯疱疹病毒在两名患者接受该药物治疗后进行了阿昔洛韦敏感性检测。在来自两名患者的分离株中，检测到敏感性有38倍和83倍的变化，同时病毒胸苷激酶活性显著降低。耐药的HSV-1分离株对Balb/C小鼠的神经毒性比患者的敏感株低约900倍，但在无毛小鼠中的皮肤毒性相似。相比之下，敏感和耐药的HSV-2分离株在致病性上没有差异。在用敏感和耐药的HSV-1分离株经口鼻接种小鼠后，在三叉神经节中检测到潜伏感染。发现来自接种耐药HSV小鼠的神经节分离株对阿昔洛韦敏感，这意味着选择了敏感表型或敏感表型发生了回复突变。接种任何一种HSV-2分离株后均未检测到三叉神经节潜伏感染。治疗期间，由于病毒胸苷激酶活性降低可产生对阿昔洛韦的耐药性，但似乎与毒力增加无关。
