Ocular HSV-1: Chromatin Remodeling in Latent TG

描述(由申请人提供)： 在工业化国家，由于复发，单纯疱疹病毒1型是造成大多数致盲角膜感染的原因。反复复发可导致不可逆转的角膜疤痕。单纯疱疹病毒在三叉神经节(TG)神经元中建立潜伏期。病毒神经再激活的分子机制(S)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，特异性的组蛋白尾部修饰是决定HSV-1基因表达的一个重要病毒转录本。为了探索参与HSV-1基因组基因调控的表观遗传因子--组蛋白乙酰化，还需要进一步的研究。这些研究将使用体内高和低表型的HSV-1毒株来比较组蛋白乙酰化与从潜伏期到再激活转变过程中病毒基因调控的关系。利用小鼠眼睛模型，我的具体目标是使用HSV-1毒株17Syn+(高表型复活剂)和F(低表型复活剂)，确定小鼠TG中四个病毒基因(DNA)在潜伏期和诱导重新激活过程中的乙酰H3关联。

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).