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: 3746538
• 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/3746538
• 关键词: chickenpox; gene expression; gene induction /repression; human tissue; latent virus infection; shingles; transcription factor; varicella zoster virus; virus genetics; virus infection mechanism

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. We are currently investigating the functions of VZV genes that regulate viral gene expression. Analysis of VZV gene products during acute infection indicate that at least five VZV genes, ORF4, ORF1O, ORF6l, ORF62, and ORF63, transactivate the expression of other VZV genes in vitro. Two of these genes (ORFlO, ORF62) activate transcription directly and their activation domains have been identified. Three of these vzv genes (ORF1O, ORF61, and ORF62) can complement the function of their herpes simplex virus homologs, while one of the genes (ORF4) cannot. Chimeric proteins, containing portions of VZV proteins and their HSV-1 homologs, have been constructed to compare functional domains of these proteins. Two VZV genes, ORF28 and ORF29, have bidirectional, overlapping promoters that regulate their expression. These control elements are activated by a viral protein (ORF62) and a cellular protein termed USF. While both of these genes are expressed in acute infection, one of the genes (ORF29) is expressed during dormant infection, while the other gene (ORF28) is not. Analysis of trigeminal ganglia from human cadavers without active evidence of VZV infection indicates that at least two VZV genes (ORF29 and ORF62) are expressed during viral latency, while other genes (ORF1O, ORF28, and ORF61) are not.

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 该项目旨在鉴定和确定VZV基因的功能， 在活跃感染期间和潜伏期在体内表达。 我们目前正在研究VZV基因的功能， 病毒基因表达 急性期VZV基因产物分析 感染表明至少五个VZV基因，ORF 4、ORF 10、ORF 61 ORF 62和ORF 63，反式激活其他VZV基因的表达， 体外 其中两个基因（ORF 10，ORF 62）直接激活转录 并且它们的激活结构域已经被鉴定。三个vzv 基因（ORF 10、ORF 61和ORF 62）可以补充它们的功能。 单纯疱疹病毒同系物，而其中一个基因（ORF 4）不能。 嵌合蛋白，含有VZV蛋白及其HSV-1的部分 同源物，以比较这些同源物的功能结构域， proteins. 两个VZV基因，ORF 28和ORF 29，具有双向重叠启动子， 来调节它们的表达。 这些控制元件被激活， 病毒蛋白（ORF 62）和称为USF的细胞蛋白。 虽然双方 这些基因在急性感染中表达，其中一个基因（ORF 29）是 在休眠感染期间表达，而另一个基因（ORF 28）不表达。 无活动证据人尸三叉神经节分析 表明至少有两个VZV基因（ORF 29和ORF 62） 在病毒潜伏期期间表达，而其他基因（ORF 10、ORF 28和 ORF 61）没有。