Virulence Genes in Herpes Simplex Virus Ocular Infection

描述(申请人提供)：单纯疱疹病毒1型(HSV-1)是一种重要的人类病原体，可引起皮肤粘膜溃疡、角膜炎和脑炎等疾病。在美国，HSV-1是导致感染致盲的首要原因，也是导致散发性脑炎的首要原因。HSV-1毒株表现出从没有疾病到致命脑炎的毒力模式。角膜炎的严重程度在不同的病毒株之间也有很大差异。到目前为止，人们对大多数HSV-1基因在感染严重程度中所起的作用知之甚少。很可能是 毒力差异是由于多个基因和给定病毒株携带的等位基因组合的影响。研究病毒基因对毒力影响的传统方法 不能识别多个基因的影响。我们能够通过在两个毒株之间进行混合感染来产生重组HSV-1毒株，并发现这些重组体的毒力表型有很大的差异。这项研究的总体目标是将我们分离具有不同疾病表型的重组病毒的能力与我们使用下一代测序方法和对亲本株之间的SNPs进行新的统计分析的经验相结合，以确定对眼部HSV-1感染至关重要的毒力因素 还有脑炎。这一非常新颖的方法将使我们能够确定多个 基因在毒力中的作用，并可能确定上位性在决定给定病毒的毒力表型中的作用。

DESCRIPTION (provided by applicant): Herpes simplex virus type 1 (HSV-1) is a significant human pathogen causing diseases such as mucocutaneous ulcers, keratitis, and encephalitis. In the USA, HSV-1 is the leading cause of blindness due to infection and the leading cause of sporadic encephalitis. Strains of HSV-1 display virulence patterns ranging from no disease to lethal encephalitis. The severity of keratitis also varies widely between viral strains. To date, little is known about role most HSV-1 genes play in the severity of an infection. It is likely that virulence differences are due to effects of multiple genes and the combination of alleles carried by a given strain of virus. Traditional methods for studying the effect of viral genes on virulence are not capable of identifying the effects of multiple genes. We are capable of generating recombinant HSV-1 strains by carrying out mixed infections between two strains and have found that these recombinants can vary widely in their virulence phenotypes. The overall goal of this study is to combine our ability to isolate recombinant viruses with varying disease phenotypes with our experience using next generation sequencing methods and novel statistical analysis of SNPs between the parental strains to identify virulence factors critical for ocular HSV-1 infection and encephalitis. This highly novel approach will allow us to identify the contribution of multiple genes in virulence and potentially identify a role for epistasis in determining the virulence phenotype of a given virus.