Bevilacqua F, Davis-Poynter N, Worrallo J, Gower D, Collins P, Darby G
Deaprtment of Molecular Biology, Wellcome Research Laboratories, Beckenham, Kent, UK.
J Gen Virol. 1995 Aug;76 ( Pt 8):1927-35. doi: 10.1099/0022-1317-76-8-1927.
A recombinant of herpes simplex virus (HSV) was constructed in which the HSV thymidine kinase (TK) gene was deleted and the varicella-zoster virus (VZV) TK gene was introduced into the US5 region under the control of the human cytomegalovirus IE promoter. Infection with the recombinant (R18) led to the induction of TK although the kinetics of synthesis resembled those of a 'late' gene product. The recombinant was virulent in the zosteriform mouse model with the pattern of pathogenesis similar to that of wild-type HSV-1. The sensitivity of the recombinant to several nucleoside analogues was assessed and in most cases (BVaraU, ACV and GCV) it resembled VZV rather than HSV. The enhanced sensitivity of the recombinant to BVaraU compared with wild-type HSV resulted in a far greater response to treatment with BVaraU as assessed in the mouse model.
构建了一种单纯疱疹病毒（HSV）重组体，其中HSV胸苷激酶（TK）基因被删除，水痘带状疱疹病毒（VZV）TK基因在人巨细胞病毒IE启动子的控制下被引入US5区域。用该重组体（R18）感染可诱导TK产生，尽管其合成动力学类似于“晚期”基因产物。该重组体在带状疱疹样小鼠模型中具有致病性，其发病模式与野生型HSV-1相似。评估了该重组体对几种核苷类似物的敏感性，在大多数情况下（BVaraU、ACV和GCV），它类似于VZV而非HSV。与野生型HSV相比，该重组体对BVaraU的敏感性增强，在小鼠模型中评估显示，其对BVaraU治疗的反应要大得多。
