MOLECULAR ANALYSIS OF NEURONAL HSV LATENCY/REACTIVATION

神经元 HSV 潜伏期/再激活的分子分析

基本信息

批准号：
2065156
负责人：
Lawrence Raymond Stanberry
金额：
$ 14.85万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-03-01 至 1995-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2065156
关键词：
disease /disorder model genital herpes guinea pigs herpes simplex virus 1 herpes simplex virus 2 latent virus infection molecular pathology northern blottings relapse /recurrence spinal ganglion virulence virus DNA

项目摘要

Recurrent herpes simplex virus (HSV) infections afflict millions of Americans producing significant physical and psychological morbidity, serving as an important source of communicable virus, and causing potentially life-threatening disease in the immunocompromised patient. Recurrent infections result from the reactivation is limited, with most research having focused on HSV type 1. The objective of this proposal is to explore the molecular events associated with HSV type 2 latency, reactivation and recurrence. The proposed research will use an experimental genital HSV infection of guinea pigs which has proven to be a unique self-limited vaginitis, latent infection of sensory ganglia, and both spontaneous and inducible recurrent disease. Polymerase chain reaction amplification and in situ hybridization will be used to characterize HSV-1 and HSV-2 transcription in latently infected sensory ganglia. The pattern of transcription will be correlated with the ability of the virus type to produce recurrent disease. Recently, UV irradiation has been shown to predictably induce recurrent genital herpes in latently infected guinea pigs. This model will be used to explore the molecular events associated with the reactivation of latent virus by using Northern blot/in situ hybridization and a genetically engineered HSV-2 mutant expressing the lac Z gene under the control of a late gene promoter. A limited region of the HSV-1 genome is transcribed during latent infection however, mutants deleted of this region are still capable of establishing and maintaining a latent infection. By ascertaining if such mutants can produce spontaneous and/or induced recurrent genital herpes in guinea pigs it will be possible to explore whether latency associated transcripts are important in the produce recurrent genital infections will be explored using intertypic HSV-1 X HSV-2 mutants. Molecular analyses of these mutants will define the regions of the HSV-2 genome responsible for recurrent genital herpes. The long term goal of this proposal is to expand our understanding of the pathophysiology of latent and recurrent HSV infections which will ultimately lead to new strategies for the control of an exceedingly common public health problem.

复发性疱疹单纯疱疹病毒（HSV）感染折磨数百万美国人产生重大的身体和心理发病率，作为传染病的重要来源，并导致免疫功能低下的患者潜在威胁生命的疾病。重新激活引起的复发感染受到限制，大多数研究专注于HSV类型1。该提案的目的是探索与HSV 2型潜伏期相关的分子事件，重新激活和复发。拟议的研究将使用豚鼠的实验生殖器HSV感染已被证明是独特的自限性阴道炎，感官神经节的潜在感染和自发和可诱导的复发性疾病。聚合酶链反应扩增和原位杂交将用于表征在潜在感染的感觉中的HSV-1和HSV-2转录神经节。转录模式将与能力相关病毒类型产生复发性疾病。最近，紫外线照射已经显示出可以预见的诱导潜在的复发生殖器疱疹被感染的豚鼠。该模型将用于探索分子通过使用北部与潜在病毒重新激活相关的事件印迹/原位杂交和基因设计的HSV-2突变体在晚期基因启动子的控制下表达LAC Z基因。一个 HSV-1基因组的有限区域在潜在感染期间转录但是，该区域删除的突变体仍然能够建立并保持潜在感染。通过确定此类突变体是否可以在豚鼠中产生自发和/或诱发的复发性生殖器疱疹可以探索是否相关的成绩单是在农产品中重要的生殖器感染很重要使用型中型HSV-1 X HSV-2突变体。这些分子分析突变体将定义负责HSV-2基因组的区域经常性生殖器疱疹。该提议的长期目标是扩展我们对潜在和经常性HSV的病理生理学的理解最终将导致控制的新策略的感染一个非常普遍的公共卫生问题。