THE GENETICS OF HSV-1 REACTIVATION

单纯疱疹病毒I型(HSV-1)通过口腔感染人类，导致口腔牙周炎和眼角膜炎。HSV-1感染在人群中高度流行。在美国，大约80%的成年人是HSV-1血清阳性。在初次感染之后，这种病毒建立了三叉神经的潜伏感染，从中可以重新激活，从而导致疾病的复发。我们目前在分子水平上对潜伏期和再激活的发病机制的了解是不完整的。到目前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，LAT区域对重新激活的作用还没有明确的分子作用，也没有确定LAT区域在建立潜伏感染中的作用。这一提议的目的是在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个功能上存在缺陷。该提案的第二个目标是使用各种基于聚合酶链式反应和非聚合酶链式反应的技术来研究与野生型病毒相比，这些突变病毒建立潜伏感染的能力。最后一个感兴趣的领域是构建不能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区域如何对重新激活事件做出贡献。

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.