MOLECULAR BIOLOGY OF VARICELLA ZOSTER VIRUS INFECTION

水痘带状疱疹病毒感染的分子生物学

• 批准号: 2566771
• 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/2566771
• 关键词: Herpesviridae; Pan; chickenpox; gene expression; human genetic material tag; human tissue; latent virus infection; postmortem; transcription factor; varicella zoster virus; virus DNA; virus genetics; virus infection mechanism; virus protein

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. VZV genes that are expressed during active infection and regulate viral gene expression in vitro are being studied. VZV encodes five proteins (ORF4, 10, 61, 62, 63) that regulate expression of other VZV genes in vitro. A transcriptional activation domain in the VZV ORF10 protein was identified. Using a computer program (hydrophobic cluster analysis) we were able to identify domains in other herpesviruses that can also activate transcription. The VZV ORF10 protein was shown to interact with two cellular proteins (Oct1, HCF). This interaction allows the ORF10 protein to activate transcription of VZV ORF62. An additional cellular protein (NF-Y) was shown to regulate the expression of ORF62 protein. Analysis of central nervous system tissues from human cadavers without active evidence of VZV infection indicates that at least two VZV genes (ORF29 and ORF62) are expressed while the virus is latent in the central nervous system. Two chimpanzees inoculated with VZV developed a papular rash 10 days after inoculation. VZV DNA was detected in white blood cells of both animals shortly after inoculation and in a skin biopsy from one of the animals at the time of the rash.

水痘-带状疱疹病毒（VZV）的原发性感染引起水痘， 病毒从潜伏期重新激活导致带状疱疹。 的目标 本项目的主要目的是鉴定和确定VZV基因的功能 在主动感染和潜伏感染期间表达， 身体 VZV基因在活动性感染期间表达并调节病毒 体外基因表达正在研究中。 VZV编码5种蛋白质 (ORF4，10，61，62，63），其调节其它VZV基因在 体外 VZV ORF 10蛋白中的转录激活结构域是 鉴定 使用计算机程序（疏水聚类分析），我们 能够识别出其他疱疹病毒中的结构域， 激活转录。 VZV ORF 10蛋白显示与 两种细胞蛋白（Oct 1，HCF）。 这种相互作用使得ORF 10 VZV ORF 62的转录。 另一种细胞 蛋白（NF-Y）对ORF 62蛋白的表达具有调控作用。 人尸体中枢神经系统组织的分析 VZV感染的活跃证据表明，至少有两个VZV基因， （ORF 29和ORF 62）表达，而病毒在中枢神经系统中潜伏。 神经系统 两只接种VZV的黑猩猩在10天后出现丘疹 接种后。 在两组的白色血细胞中均检测到VZV DNA 接种后不久的动物和来自其中一个 动物在皮疹的时候。