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，导致疾病，例如粘眼膜性溃疡，角膜炎和脑炎。在美国，HSV-1是由于感染而引起的失明的主要原因，也是零星脑炎的主要原因。 HSV-1的菌株表现出从无疾病到致命性脑炎的毒力模式。角膜炎的严重程度在病毒菌株之间也有很大差异。迄今为止，大多数HSV-1基因在感染的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作用以及给定病毒菌株携带的等位基因的组合。研究病毒基因对毒力的影响的传统方法 无法识别多个基因的影响。我们能够通过在两种菌株之间进行混合感染来产生重组HSV-1菌株，并发现这些重组者的毒力表型可能会差异很大。这项研究的总体目标是将我们的重组病毒与不同疾病表型分离的能力与我们使用下一代测序方法的经验以及父母菌株之间SNP的新统计分析，以识别对眼部HSV-1感染至关重要的毒力因子的新统计分析 和脑炎。这种高度新颖的方法将使我们能够确定多重的贡献 毒力中的基因并有可能识别上毒在确定给定病毒的毒力表型中的作用。