HSV-1 GENE EXPRESSION IN LATENTLY INFECTED NEURONS

潜伏感染神经元中的 HSV-1 基因表达

• 批准号: 3142780
• 负责人: LAWRENCE T FELDMAN
• 金额: $ 15.65万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142780
• 关键词: HeLa cells; Herpes simplex disease; gene deletion mutation; gene expression; genetic promoter element; genetic recombination; genetic transcription; herpes simplex virus 1; immunofluorescence technique; in situ hybridization; laboratory mouse; latent virus infection; molecular cloning; neurons; nucleic acid sequence; polyadenylate; tissue /cell culture; virus cytopathogenic effect; virus genetics; virus infection mechanism

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.

这项建议的主要目的是了解几个关键基因是如何在基因组中表达的。 单纯疱疹病毒在潜伏状态下受到调节。 使用许多 重组病毒和建立急性和潜伏感染， 小鼠神经节，这项建议将调控基因编码的 LAT转录物，以及ICP 0和ICP 4蛋白的基因。 的程序 将强调在潜伏期的表达，而不是在组织中 文化这项提议的一部分是了解LAT基因是如何 转录、加工并运输到细胞质。 第二部分 这一建议的目的是确定启动子的位置和 对神经元中的转录起重要作用的元件。一套重要的 在潜伏期不转录的启动子是一组即时-早期启动子。 发起人。他们没有抄写的原因是 研究了最后，建议修改两个 潜伏期内重要的即刻早期基因。 使用启动子， 在神经元中是活跃的，ICP 0和ICP 4的基因将被表达， 评价每种重组病毒在潜伏期期间的表型。 这些研究应有助于了解 在潜伏感染期间进行手术 这些长期目标 研究的目的是了解分子基础的机制， 规范建立、维护和激活潜在的 状态