MOLECULAR BIOLOGY OF VARICELLA ZOSTER VIRUS INFECTIONS

1)水痘带状疱疹病毒(VZV)的初次感染导致 水痘，从潜伏期重新激活病毒会导致带状疱疹。 该项目的目标是确定和确定 在活动性感染和潜伏期表达的VZV基因 在身体里。 2)在活动性感染过程中表达并调节的VZV基因 病毒基因的体外表达正在研究中。VZV基因分析 急性感染期间的产物显示，VZV的五个基因ORF4， ORF10、ORF61、ORF62和ORF63调节其他VZV的表达 基因在体外。两种细胞蛋白(Oct1，hcf)已经被证明是 与VZV蛋白(ORF10)相互作用激活ORF62基因。这些 细胞蛋白已被证明与细胞上的特定序列结合 VZV ORF62启动子。发现了一种不同的细胞蛋白(USF) 与另一种VZV蛋白(ORF62)相互作用以激活其表达 2个VZV基因(ORF28、ORF29)。USF蛋白与一种特定的 序列位于ORF 28和29基因之间。 3)两个VZV基因(VZV ORF4)活性所需的关键结构域 和ORF61)已被鉴定。氨基末端附近的结构域 ORF4是激活其他VZV基因表达所必需的。此域 可以在功能上替代疱疹中相应的同系物 单纯疱疹病毒蛋白。在无名指中发现了ORF61中的一个结构域 ORF61蛋白家族，是ORF61功能活性所必需的 蛋白。ORF10的转录激活结构域已被 在蛋白质的氨基末端进行鉴定。此激活域 已被发现与其单纯疱疹病毒具有相同的结构特征 VP16同源基因。 4)中枢神经系统组织取自有 从遥远的过去的水痘感染中康复的人正在 研究以确定哪些VZV基因在病毒感染时表达 潜伏在人体内。人类三叉神经节的分析 没有VZV感染活性证据的身体表明有两个VZV ORF29和ORF62基因在非神经元的潜伏期表达 (卫星)细胞，而其他病毒基因(ORF10、ORF61)不是 表达。

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.