HSV1 ICPO AND REACTIVATION FROM LATENCY

HSV1 ICPO 和从潜伏期重新激活

• 批准号: 2708394
• 负责人: WILLIAM P HALFORD
• 金额: $ 2.62万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2708394
• 关键词: cyclophosphamide; cyclosporines; herpes simplex virus 1; immunosuppression; laboratory mouse; latent virus infection; ocular herpes; transcription factor; transfection /expression vector; trigeminal nerve; virus genetics; virus infection mechanism

The process by which herpes simplex virus type 1 (HSV-1) reactivates from latency to cause recurrent herpetic disease is poorly defined. Although considerable circumstantial evidence suggests that ICPO (an HSV-1 transactivator) plays a central role in reactivation, direct evidence to support this hypothesis is lacking. A limiting factor in the study of ICPO mutants in vivo (as with many other HSV-1 mutants) has been that ICPO mutants do not replicate as efficiently as wild-type HSV-1 in animals. Consequently, it is unclear from previous analyses if the decreased reactivation of ICPO- mutant viruses from trigeminal ganglion is due to inefficient neuronal colonization and latent infection, or a requirement for ICPO in HSV-1 reactivation. The goals of the studies proposed herein is to a) develop methods that allow the equal establishment of latency with mutant and wild-type HSV-1 in mice, and using these methods b) obtain definitive evidence to either support or reject the hypothesis that ICPO plays a role in HSV-1 reactivation.

1 型单纯疱疹病毒 (HSV-1) 重新激活的过程 从潜伏期到引起复发性疱疹疾病的定义尚不明确。 尽管大量间接证据表明 ICPO（ HSV-1 反式激活因子）在重新激活、直接 缺乏支持这一假设的证据。 一个限制因素 ICPO 突变体的体内研究（与许多其他 HSV-1 突变体一样） ICPO 突变体的复制效率不如野生型 动物中的 HSV-1。因此，从之前的分析来看，尚不清楚是否 来自三叉神经的 ICPO 突变病毒的重新激活减少 神经节是由于低效的神经元定植和潜在的 感染，或 HSV-1 重新激活中 ICPO 的要求。 目标 本文提出的研究的目的是 a) 开发允许 在小鼠中与突变型和野生型 HSV-1 建立相同的潜伏期， 并使用这些方法 b) 获得明确的证据来支持 或拒绝 ICPO 在 HSV-1 重新激活中发挥作用的假设。