ANALYSIS OF HOMOLOGOUS RECOMBINATION IN HSV 1

这项研究提案的长期目标是定义不良的 单纯疱疹病毒同源重组的特征性机制 1型病毒(HSV-1)。更好地理解基本知识的这一方面 对这种重要病原体的生物学研究可能有助于更有效地 治疗策略。在这方面有三个具体的目标 开发HSV-1 DNA复制蛋白能力的建议 以介导同源重组。首先，重组的HSV-1将被 在L-S交界处生成了缺乏阿尔法序列的序列，并进行了测试 进行基因组异构化的能力。二、机制 由双链断裂引起的同源重组 EcoRI和细胞拓扑异构酶II将被研究。最后， 重组人单纯疱疹病毒1型复制蛋白表达能力的研究 杆状病毒在Sf9细胞中介导同源重组将是 检测并与HSV-1介导的反应进行比较；该系统将 也可以用来确定HSV-1是否参与复制- 依赖-~重组或重组-依赖复制。这些 这些结果将有助于阐明同源重组的机制 在HSV-1和NAI中提供了对人类这一现象的重要见解 细胞。

The long-term objective of this research proposal is to define the poorly characterized mechanism of homologous recombination in Herpes Simplex Virus Type 1 (HSV-1). A better understanding of this aspect of the basic biology of this important pathogen may contribute to more effective therapeutic strategies. Three specific aims are being undertaken in this proposal that exploit the ability of the HSV-1 DNA replication proteins to mediate homologous recombination. First, a recombinant HSV-1 will be generated that lacks the alpha sequence at the L-S junction and tested for the ability to undergo genome isomerization. Second, the mechanism of homologous recombination induced by double-strand breaks generated by EcoRI and cellular topoisomerase II will be investigated. Finally, the ability of the HSV-1 replication proteins expressed by recombinant baculoviruses in Sf9 cells to mediate homologous recombination will be examined and compared with reactions mediated by HSV- 1; this system will also be used to determine if HSV- 1 participates in replication- dependent-~recombination or recombination-dependent-replication. These results will help to elucidate the mechanism of homologous recombination in HSV-1 and nay provide important insight into this phenomenon in human cells.