HSV-1 GENE EXPRESSION IN LATENTLY INFECTED NEURONS

这项提议的广泛目标是了解几个关键基因是如何 单纯疱疹病毒处于潜伏状态。使用数字 重组病毒和建立急性和潜伏感染 小鼠神经节，这一建议将编码基因的调控 Lat转录本，ICPO和ICP4蛋白基因。程序 将强调潜伏期的表达，而不是在组织中的表达 文化。这项建议的一部分是了解LAT基因是如何 转录、加工并运输到细胞质。第二部分 这项建议的目的是确定发起人的位置和 在神经元中对其转录起重要作用的元件。一组重要的 潜伏期内未转录的启动子是一组立即-早期 推动者。他们没有转录的原因将是 调查过了。最后，建议改变两个词的表达方式 潜伏期内重要的即刻早期基因。使用发起人，其中 在神经元中是活跃的，ICPO和ICP4的基因将被表达和 将评估每个重组病毒在潜伏期的表型。 这些研究应该有助于理解 是在潜伏感染期间运作的。这些项目的长期目标是 研究是为了了解分子基础的机制， 规范潜伏期的建立、维护和复活 州政府。

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.