Virulence Genes in Herpes Simplex Virus Ocular Infection

单纯疱疹病毒眼部感染的毒力基因

• 批准号: 8481769
• 负责人: Curtis R Brandt
• 金额: $ 46.56万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8481769
• 关键词: Affect; Alleles; Blepharitis; Blindness; Brain; Cessation of life; Clinical; Cornea; Corneal Neovascularization; Data; Databases; Disease; Encephalitis; Eye Infections; Gene Combinations; Genes; Genetic; Genetic Engineering; Genetic Epistasis; Genome; Genomics; Goals; Growth; Hand; Herpesvirus 1; Herpetic Keratitis; Human; Infection; Inherited; Keratitis; Link; Maps; Methods; Nature; Outcome; Pattern; Phenotype; Play; Point Mutation; Property; Recombinants; Role; Severities; Simplexvirus; Statistical Methods; Structure of trigeminal ganglion; Testing; Time; Ulcer; Viral; Viral Genes; Virulence; Virulence Factors; Virus; Virus Diseases; disease phenotype; experience; insight; next generation sequencing; novel; novel strategies; pathogen; public health relevance; recombinant virus

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.

描述（由申请人提供）：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是由于感染导致失明的主要原因，也是散发性脑炎的主要原因。HSV-1菌株的毒力模式从不致病到致死性脑炎不等。角膜炎的严重程度在病毒株之间也有很大差异。迄今为止，人们对大多数HSV-1基因在感染严重程度中的作用知之甚少。很可能 毒力差异是由于多个基因的影响和给定病毒株携带的等位基因的组合。研究病毒基因对毒力影响的传统方法 无法识别多个基因的影响。我们能够通过在两种毒株之间进行混合感染来产生重组HSV-1毒株，并且已经发现这些重组体在其毒力表型上可以有很大的不同。本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亲本菌株之间SNP的新统计分析的经验相结合，以鉴定对眼部HSV-1感染至关重要的毒力因子 和脑炎。这种非常新颖的方法将使我们能够确定多个因素的贡献。 基因在毒力中的作用，并可能确定上位性在确定给定病毒的毒力表型中的作用。