Ocular HSV-1: Chromatin Remodeling in Latent TG

眼部 HSV-1：潜伏 TG 中的染色质重塑

• 批准号: 6952743
• 负责人: DONNA M NEUMANN
• 金额: $ 4.4万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 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/6952743
• 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

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）： HSV-1是工业化国家中由于复发导致的大多数致盲性角膜感染的原因。反复复发可导致不可逆的角膜瘢痕形成。HSV在三叉神经节（TG）的神经元中建立潜伏期。病毒神经再激活的分子机制尚不清楚。组蛋白乙酰化和去乙酰化在转录调控中起重要作用，最近的证据表明，特异性组蛋白尾部修饰是HSV-1基因表达的决定因素。为了探索一个表观遗传因子，组蛋白乙酰化，参与基因调控的HSV-1基因组，需要进一步的研究。这些研究将使用高和低体内表型再活化剂的HSV-1菌株，比较从潜伏期到再活化过渡期间与病毒基因调控相关的组蛋白乙酰化。使用小鼠眼模型，我的具体目标是使用HSV-1株17 Syn+（高表型再激活因子）和F（低表型再激活因子）确定小鼠TG中四种病毒基因（DNA）在潜伏期和诱导再激活中的乙酰基H3关联。