LATENT VIRUS INFECTION AND REACTIVATION

潜伏病毒感染和重新激活

• 批准号: 3401225
• 负责人: Richard B. Tenser
• 金额: $ 10.58万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3401225
• 关键词: autoradiography; gene complementation; genetic manipulation; herpes simplex virus 1; herpes simplex virus 2; in situ hybridization; laboratory mouse; latent virus infection; temperature sensitive mutant; thymidine kinase; tissue /cell culture; virus RNA; virus genetics; virus infection mechanism; virus replication

We have shown that herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) expression is important for HSV latency. Latency was defined by the usual criterion of the isolation of infectious virus during the period of latent infection. For the isolation of the virus it is necessary that (1) the latent infection be established and (2) that infectious virus can be reactivated. In the present proposal we plan to differentiate between the role of HSV TK expression for the establishment of latency and for the reactivation of the latent virus. To perform this detailed investigation of the mechanisms of latency we will perform studies with a temperature sensitive TK- mutant of HSV-1 and a mutant of HSV-1 containing a defined deletion in the TK gene. Studies will also be performed with TK mutants of HSV-2, including a deletion mutant to determine the importance of TK expression in the pathogenesis of infection. In vivo complementation to determine latency established by TK- HSV, rescue of the TK- HSV during latency, and detection of TK- HSV by in situ hybridization will be evaluated. In situ hybridization methodology will also be employed to investigate the presence of HSV specified RNA, including that for TK activity during latency. Finally, methods to inhibit and to chronize HSV reactivation will be utilized to permit study of the reactivation process. These detailed studies of the establishment of HSV latency and of reactivation will provide insights into the mechanisms of these processes.

我们已经证明了单纯疱疹病毒1型(HSV-1)胸苷激酶 (TK)表达对HSV潜伏期有重要影响。延迟由 流行性出血热期间传染性病毒分离的常用标准 潜伏感染。为了分离病毒，有必要(1) 以及(2)传染性病毒可以是 重新启动。在本提案中，我们计划区分 单纯疱疹病毒TK的表达在建立潜伏期和 潜伏病毒的重新激活。进行这项详细的调查 对于潜伏期的机制，我们将用温度进行研究 HSV-1敏感TK突变体和HSV-1突变体 TK基因缺失。还将对Tk突变体进行研究 HSV-2，包括一个确定TK重要性的缺失突变体 在感染发病机制中的表达。体内互补作用 确定TK-HSV建立的潜伏期，抢救TK-HSV 潜伏期和原位杂交检测TK-HSV 已评估。还将使用原位杂交方法来 调查HSV特异性RNA的存在，包括TK的RNA 延迟期间的活动。最后，抑制和计时HSV的方法 将利用重新激活来研究重新激活过程。 这些关于建立HSV潜伏期和 重新激活将提供对这些过程的机制的洞察。