HSV-1 GENE EXPRESSION IN LATENTLY INFECTED NEURONS

该提案的主要目标是了解几个关键基因如何 单纯疱疹病毒在潜伏状态下受到调节。 使用号码 重组病毒并在体内建立急性和潜伏感染 小鼠神经节，该提案将调节编码基因 LAT 转录本，以及 ICPO 和 ICP4 蛋白的基因。 程序 将强调潜伏期的表达，而不是组织中的表达 文化。该提案的一部分是了解 LAT 基因是如何发挥作用的 转录、加工并运输至细胞质。 第二部分 该提案的目的是确定发起人的位置和 对其在神经元中转录至关重要的元件。一组重要的 潜伏期不转录的启动子是立即早期启动子的集合 发起人。它们缺乏转录的原因是 调查了。最后，建议修改两个表达式 潜伏期重要的即早基因。 使用促进剂 在神经元中活跃，ICPO 和 ICP4 的基因将被表达并且 将评估每种重组病毒在潜伏期的表型。 这些研究应有助于理解其机制 正在潜伏感染期间进行操作。 这些的长期目标 研究的目的是了解其机制的分子基础 调节潜在的建立、维持和重新激活 状态。

The broad aim of this proposal is to understand how several key genes of herpes simplex virus are regulated in the latent state. Using a number of recombinant viruses and establishing acute and latent infections in mouse ganglia, this proposal will the regulation of genes encoding the LAT transcript, and the genes for ICPO and ICP4 proteins. The procedures will emphasize the expression during latency, rather than in tissue culture. A part of this proposal is to understand how the LAT gene is transcribed, processed, and transported to the cytoplasm. A second part of this proposal is to determine the location of the promoter and the elements important for its transcription in neurons. An important set of promoters not transcribed during latency is the set of immediate-early promoters. The reason for their lack of transcription will be investigated. Finally, it is proposed to alter the expression of two important immediate-early genes during latency. Using promoters which are active in neurons, the genes for ICPO and ICP4 will be expressed and the phenotype of each recombinant virus during latency will be evaluated. These studies should facilitate an understanding of the mechanisms which are operating during a latent infection. The long term goal of these studies is to understand the molecular basis for the mechanisms which regulate the establishment, maintenance, and reactivation the latent state.