GENE EXPRESSION DURING HSV-1 LATENCY AND REACTIVATION

HSV-1 潜伏期和重新激活期间的基因表达

• 批准号: 6651792
• 负责人: NIGEL William FRASER
• 金额: $ 20.08万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651792
• 关键词: Herpes simplex disease; RNA splicing; disease /disorder model; gene deletion mutation; gene expression; genetic mapping; genetic promoter element; genetic regulation; genome; herpes simplex virus 1; introns; laboratory mouse; latent virus infection; messenger RNA; neurons; neurotropic virus; polymerase chain reaction; protein structure function; regulatory gene; tissue /cell culture; transcription factor; virulence; virus RNA; virus genetics; virus infection mechanism; virus protein

Description (provided by applicant) Human neurotropic herpes viruses, such as HSV, cause much disease and suffering. The long-term objective of this project is to understand the mechanism of Herpes Simplex Virus latency and reactivation at the molecular level. In the present application, we propose to continue to examine the Latency Associated Transcripts (LATs), and genes in the region of the genome encoding the LATs, to determine what role they play in viral latency and reactivation. These goals will be achieved by using the techniques of molecular virology and a mouse model of infection and latency. In the first specific aim, we will map and characterize transcripts from the region immediately upstream of the LAT promoter. Preliminary evidence suggest that there is a virulence gene encoded in this region. In the second aim, we will study the functionality of the LAT mRNA and 2kb LAT intron. There has been little study of the LAT mRNA, most effort being focused on the 2kb RNA, which is now recognized as an intron. The 2kb LAT intron is found in the nucleus of latently infected neurons, yet in the cytoplasm of lytically-infected cells. What determines the cellular distribution of LAT? The 2kb LAT intron appears in the cytoplasm during lytic infection, yet does not appear to be translated. Does it serve a function like aiding in splicing and export from the nucleus? We will attempt to study LAT function through understanding its structure and the proteins associated with it. In the third specific aim, we will study the mechanism of reactivation and attempt to determine what type of cell factors are involved. Recently, we showed that immediate-early genes do not appear before early genes during reactivation, suggesting that some cellular factor up-regulates, both immediate early and early classes of genes, rather than specifically upregulating immediate-early genes, as is seen during primary infection. These studies will continue our methodical investigation of herpes simplex virus latency and reactivation, and the role of the LAT gene in these processes.

描述（由申请人提供） 人类神经性疱疹病毒，例如HSV，引起很多疾病， 痛苦。该项目的长期目标是了解 单纯疱疹病毒潜伏期的机理和分子的重新激活 等级。 在本应用程序中，我们建议继续检查潜伏期 相关的转录本（LATS）和基因组编码区域的基因 LATS，确定它们在病毒潜伏期和重新激活中的作用。 这些目标将通过使用分子病毒学技术来实现和 小鼠感染和潜伏期的模型。在第一个特定目标中，我们将映射 并表征来自LAT上游的区域的成绩单 发起人。初步证据表明有一个毒力基因编码 在这个地区。在第二个目标中，我们将研究LAT的功能 mRNA和2KB LAT内含子。对LAT mRNA的研究很少，大多数 努力专注于2KB RNA，现在被认为是内含子。这 2KB LAT内含子在潜在感染神经元的核中发现，但在 脊柱感染细胞的细胞质。什么决定了细胞 拉特分布？ 2KB LAT内含子在裂解过程中出现在细胞质中 感染，但似乎没有翻译。它是否具有像 协助剪接并从细胞核中出口？我们将尝试研究LAT 通过了解其结构和与之相关的蛋白质的功能 它。在第三个特定目的中，我们将研究重新激活的机制和 尝试确定涉及哪种类型的细胞因素。最近，我们 表明在早期基因之前没有立即出现基因 重新激活，表明某些细胞因子上调，都立即 基因的早期和早期类别，而不是专门上调 正如原发性感染期间看到的那样，立即的基因。这些研究会 继续我们对单纯疱疹病毒潜伏期和 重新激活以及LAT基因在这些过程中的作用。