Ocular HSV-1: Chromatin Remodeling in Latent TG

眼部 HSV-1：潜伏 TG 中的染色质重塑

基本信息

批准号：
6890615
负责人：
DONNA M NEUMANN
金额：
$ 4.11万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-30 至 2007-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6890615
关键词：
acetylation chromatin chromatin immunoprecipitation disease /disorder model ganglions gene expression genetic transcription herpes simplex virus 1 histones laboratory mouse latent virus infection ocular herpes postdoctoral investigator relapse /recurrence trigeminal nerve virus DNA virus genetics virus infection mechanism

项目摘要

DESCRIPTION (provided by applicant): HSV-1 is responsible for the majority of blinding corneal infections in industrialized countries due to recurrences. Repeated recurrences can lead to irreversible corneal scarring. HSV establishes latency in neurons in the trigeminal ganglia (TG). The molecular mechanism(s) underlying viral neural reactivation are not known. Histone acetylation and deacetylation have been shown to play important roles in transcriptional regulation and recent evidence has shown that specific histone tail modification acts as a determinant for HSV-1 gene expression of one important viral transcript. To explore one epigenetic factor, histone acetylation, involved in gene regulation of the HSV-1 genome, further studies are needed. These studies will employ the use of HSV-1 strains that are high and low in vivo phenotypic reactivators to compare the histone acetylation in relation to viral gene regulation during the transition from latency to reactivation. Using the mouse eye model, my specific goals are to determine the acetyl H3 association of four viral genes (DNA) in the mouse TG in latency and induced reactivation, using the HSV-1 strains 17Syn+ (high phenotypic reactivator) and F (low phenotypic reactivator).

描述（由申请人提供）：由于复发，HSV-1负责工业化国家的大多数角膜感染。重复复发会导致不可逆的角膜疤痕。 HSV在三叉神经节（TG）中建立了神经元的潜伏期。尚不清楚基于病毒神经重新激活的分子机制。组蛋白乙酰化和脱乙酰化已被证明在转录调节中起重要作用，并且最近的证据表明，特定的组蛋白尾巴修饰充当了一种重要的病毒转录本的HSV-1基因表达的决定因素。为了探索一种表观遗传因素，需要进一步的研究，涉及HSV-1基因组基因调节的组蛋白乙酰化。这些研究将利用体内表型反激活剂高和低的HSV-1菌株在从潜伏期到重新激活的过渡过程中比较与病毒基因调节有关的组蛋白乙酰化。使用小鼠眼模型，我的具体目标是使用HSV-1菌株17syn+（高表型重新激活器）和F（低表型反应剂）确定潜伏期和诱导的小鼠TG中四个病毒基因（DNA）的乙酰H3缔合。