Recurrent acyclovir-resistant herpes simplex in an immunocompromised patient: Can strain differences compensate for loss of thymidine kinase in pathogenesis?
Recurrent acyclovir-resistant herpes simplex in an immunocompromised patient: Can strain differences compensate for loss of thymidine kinase in pathogenesis?
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DOI：
10.1086/515375
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发表时间：
1998-09-01
影响因子：
6.4
通讯作者：
Coen, DM
中科院分区：
文献类型：
--
作者：
Horsburgh, BC;Chen, SH;Coen, DM
为了研究抗阿昔洛韦（ACV（r））单纯疱疹病毒（HSV）如何逃避药物治疗并引起疾病，对骨髓移植（BMT）患者的HSV-1分离株进行了研究。患者在初次BMT后发生ACV（r）疾病，在第二次BMT后，尽管使用了大剂量阿昔洛韦预防，但ACV（r）HSV再次激活。每一次发病的ACV（r）分离株在病毒胸苷激酶（tk）基因中含有相同的点突变，记录了这种突变体的出现、潜伏和再激活。在敏感酶、空斑放射自显影和药物敏感性试验中，突变体的TK活性受到极大损害。然而，这些突变体和TK缺失突变体在相同的遗传背景下构建的小鼠三叉神经节中的潜伏期重新激活，与实验室菌株的类似突变体相反。假设临床分离株中的等位基因补偿了该动物模型中TK的损失，这种遗传变异性可能对人类ACV（r）疾病很重要。
To investigate how acyclovir-resistant (ACV(r)) herpes simplex virus (HSV) evades drug therapy and causes disease, HSV-1 isolates from a bone marrow transplant (BMT) patient were studied. The patient developed ACV(r) disease after an initial BMT and, following a second BMT, reactivated ACV(r) HSV despite high-dose acyclovir prophylaxis. ACV(r) isolates from each episode contained the same point mutation in the viral thymidine kinase (tk) gene, documenting the emergence, latency, and reactivation of this mutant. The mutants were exceedingly impaired for TK activity in sensitive enzyme, plaque autoradiography, and drug-susceptibility assays. Nevertheless, these mutants and a tk deletion mutant constructed in the same genetic background reactivated from latency in mouse trigeminal ganglia, in contrast to similar mutants from laboratory strains. It is hypothesized that alleles in the clinical isolate compensate for the loss of TK in this animal model, Such genetic variability may be important for ACV(r) disease in humans.