THE GENETICS OF HSV-1 REACTIVATION

单纯疱疹病毒I型（HSV-1）通过口腔感染人类，引起口腔龈口炎和眼睛角膜炎。1型单纯疱疹病毒感染在人群中非常普遍。大约80%的美国成年人对1型单纯疱疹病毒呈血清阳性反应。在原发性感染后，该病毒在三叉神经建立潜伏感染，并可重新激活，导致疾病复发。我们目前对潜伏和再激活的发病机制在分子水平上的理解是不完整的。迄今为止的研究已经确定了LAT区域在病毒从潜伏状态再激活中的重要性。然而，目前还没有明确的分子作用来确定LAT区域对再激活的贡献，也没有确定LAT区域在建立潜伏感染中的作用。该建议旨在构建更精确定义的LAT区域突变。目前的病毒突变体在不止一种功能上有缺陷。该提案的第二个目标是采用多种PCR和非PCR技术来研究这些突变病毒与野生型病毒相比建立潜伏期感染的能力。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区域如何有助于重新激活事件。

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.