MOLECULAR BIOLOGY OF VARICELLA ZOSTER VIRUS INFECTION

水痘-带状疱疹病毒(VZV)的初次感染会导致水痘， 而从潜伏期重新激活病毒会导致带状疱疹。目标 该项目的主要目的是鉴定和确定VZV基因的功能 在活动性感染期间和在潜伏期 尸体。 在活动性感染过程中表达并调节病毒的VZV基因 基因在体外的表达正在研究中。VZV编码5种蛋白质 (ORF4，10，61，62，63)，调控VZV其他基因在 体外培养。在VZV ORF10蛋白中有一个转录激活结构域 已确认身份。使用计算机程序(疏水聚类分析)，我们 能够识别其他疱疹病毒的结构域，这些结构域也可以 启动转录。VZV ORF10蛋白被证明与 两种细胞蛋白(Oct1、Hcf)。这种交互允许ORF10 激活VZV ORF62转录的蛋白质。一个额外的蜂窝 蛋白(NF-Y)对ORF62蛋白的表达有调节作用。 人身体中枢神经系统组织结构分析 VZV感染的有效证据表明，至少有两个VZV基因 (ORF29和ORF62)表达，而病毒在中央潜伏 神经系统。 两只接种VZV的黑猩猩在10天内出现丘疹 接种后。在两人的白细胞中均检测到VZV DNA 动物接种后不久，在皮肤活检中从其中一个 皮疹发生时的动物。

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.