THE GENETICS OF HSV-1 REACTIVATION

HSV-1 重新激活的遗传学

• 批准号: 6612665
• 负责人: LAWRENCE T FELDMAN
• 金额: $ 30.32万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612665
• 关键词: gene expression; gene mutation; genetic regulatory element; green fluorescent proteins; herpes simplex virus 1; introns; laboratory rabbit; lac operon; latent virus infection; pathologic process; polymerase chain reaction; relapse /recurrence; reporter genes; virus genetics; virus infection mechanism

Herpes Simplex Virus Type I (HSV-1) infects humans orofacially, causing a gingivostomatis of the mouth and a keratitis of the eye. HSV-1 infections are highly prevalent in the population. Approximately eighty percent of adults in the U.S. are seropositive for HSV-1. Following a primary infection, this virus establishes a latent infection of the trigeminal from which it can reactivate causing a recurrence of the disease. Our present understanding of the pathogenesis of both latency and reactivation at the molecular level is incomplete. Research to date has established the importance of the LAT region in viral reactivation from the latent state. However no clear molecular role for the LAT region's contribution to reactivation has been defined, nor has the role of the LAT region in establishing a latent infection been determined. This proposal is aimed at the construction of more precisely defined mutations within the LAT region. Current viral mutants are defective in more than one function. A second goal of the proposal is to employ a variety of PCR and non-PCR-based techniques to study the ability of these mutant viruses to establish a latency infection when compared with the wild type virus. The final area of interest is to construct recombinant viruses which are unable to reactivate from the latent state and to learn from the structure of those viruses how the LAT region contributes to a reactivation event.

I 型单纯疱疹病毒 (HSV-1) 感染人类口面部，引起口腔牙龈炎和眼睛角膜炎。 HSV-1 感染在人群中非常普遍。美国大约 80% 的成年人 HSV-1 血清呈阳性。原发感染后，该病毒会在三叉神经中建立潜伏感染，并可重新激活，导致疾病复发。 我们目前在分子水平上对潜伏期和再激活发病机制的理解并不完整。 迄今为止的研究已经确定了 LAT 区域在病毒从潜伏状态重新激活中的重要性。 然而，尚未确定 LAT 区域对重新激活的贡献的明确分子作用，也未确定 LAT 区域在建立潜伏感染中的作用。该提案旨在在 LAT 区域内构建更精确定义的突变。 目前的病毒突变体在不止一种功能上存在缺陷。 该提案的第二个目标是采用各种基于 PCR 和非 PCR 的技术来研究这些突变病毒与野生型病毒相比建立潜伏感染的能力。 最后一个感兴趣的领域是构建无法从潜伏状态重新激活的重组病毒，并从这些病毒的结构中了解 LAT 区域如何促进重新激活事件。