MOLECULAR BIOLOGY OF VARICELLA ZOSTER VIRUS INFECTIONS

水痘带状疱疹病毒感染的分子生物学

• 批准号: 5200468
• 负责人: J I COHEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200468
• 关键词: chickenpox; gene expression; gene induction /repression; human genetic material tag; latent virus infection; shingles; transcription factor; varicella zoster virus; virus genetics; virus infection mechanism

1) Primary infection with varicella-zoster virus (VZV) causes chickenpox, and reactivation of the virus from latency results in zoster. The goals of this project are to identify and determine the function of VZV genes that are expressed during active infection and during latency in the body. 2) VZV genes that are expressed during active infection and regulate viral gene expression in vitro are being studied. Analysis of VZV gene products during acute infection indicate that five VZV genes, ORF4, ORF10, ORF61, ORF62, and ORF63, regulate the expression of other VZV genes in vitro. Two cellular proteins (Oct1, HCF) have been shown to interact with a VZV protein (ORF10) to activate the ORF62 gene. These cellular proteins have been shown to bind to a specific sequence on the VZV ORF62 promoter. A different cellular protein (USF) has been found to interact with another VZV protein (ORF62) to activate expression of two VZV genes (ORF28, ORF29). The USF protein binds to a specific sequence located between the ORF 28 and 29 genes. 3) Critical domains required for the activity of two VZV genes (VZV ORF4 and ORF61) have been identified. A domain near the amino terminus of ORF4 is required to activate expression of other VZV genes. This domain can functionally substitute for its corresponding homolog in a herpes simplex virus protein. A domain in ORF61 is found in the RING finger family of proteins and is required for functional activity of ORF61 protein. The transcription activation domain of ORF10 has been identified at the amino terminus of the protein. This activation domain has been found to share structural features with its herpes simplex virus VP16 homolog. 4) Central nervous system tissues obtained from individuals who have recovered from chicken pox infection in the distant past are being studied to determine which VZV genes are expressed while the virus in dormant in the human body. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that two VZV genes, ORF29 and ORF62, are expressed during latency in non-neuronal (satellite) cells, while other viral genes (ORF10, ORF61) are not expressed.

1)水痘-带状疱疹病毒（VZV）的主要感染原因 水痘，病毒因潜伏期而重新激活，导致带状疱疹。 本项目的目标是确定和确定 VZV基因在活跃感染期间和潜伏期期间表达 在体内 2)VZV基因在活动性感染期间表达并调节 正在研究体外病毒基因表达。 VZV基因分析 急性感染期间的产物表明，VZV的五个基因，ORF4， ORF10、ORF61、ORF62和ORF63调节其他VZV的表达 体外基因。 两种细胞蛋白（Oct1，HCF）已被证明 与VZV蛋白（ORF10）相互作用以激活ORF62基因。 这些 细胞蛋白质已被证明与细胞表面的特定序列结合。 VZV ORF 62启动子。 发现了一种不同的细胞蛋白（USF） 与另一种VZV蛋白（ORF62）相互作用， 2个VZV基因（ORF28、ORF29）。 USF蛋白结合到一个特定的 位于ORF 28和29基因之间的序列。 3)两个VZV基因（VZV ORF4）活性所需的关键结构域 和ORF61）已经被鉴定。 氨基末端附近的结构域 ORF4需要激活其他VZV基因的表达。 此域 可以在功能上替代疱疹病毒中相应的同源物 单纯病毒蛋白 ORF61中的一个结构域存在于RING指中， 是ORF61功能活性所必需的蛋白质家族 蛋白 ORF10的转录激活结构域已经被发现， 在蛋白质的氨基末端鉴定。 该激活域 与单纯疱疹病毒有着共同的结构特征 VP16同源物。 4)从患有以下疾病的个体中获得的中枢神经系统组织 在遥远的过去从水痘感染中恢复过来的人 研究以确定哪些VZV基因表达，而病毒在 潜伏在人体内 人三叉神经节的分析 没有VZV感染的活跃证据的尸体表明，两个VZV 基因ORF29和ORF62在非神经元细胞的潜伏期表达， （卫星）细胞，而其他病毒基因（ORF10，ORF61）不是 表达。