Recurrent acyclovir-resistant herpes simplex in an immunocompromised patient: Can strain differences compensate for loss of thymidine kinase in pathogenesis?

Brian C. Horsburgh, Shun Hua Chen, André Hu, Gilbert B. Mulamba, William H. Burns, Donald M. Coen

研究成果: Article同行評審

54 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)618-625
頁數8
期刊Journal of Infectious Diseases
178
發行號3
DOIs
出版狀態Published - 1998

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 傳染性疾病

指紋

深入研究「Recurrent acyclovir-resistant herpes simplex in an immunocompromised patient: Can strain differences compensate for loss of thymidine kinase in pathogenesis?」主題。共同形成了獨特的指紋。

引用此