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: 3790753
• 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/3790753
• 关键词: clone cells; gene expression; gene mutation; genetic mapping; genetic transcription; in situ hybridization; latent virus infection; molecular pathology; northern blottings; regulatory gene; trigeminal nerve; varicella zoster virus; virus genetics; virus infection mechanism; virus protein

Varicella-zoster virus causes chickenpox on primary infection, and zoster during reactivation from viral latency. The goals of this project are to identify and determine the function of varicella-zoster virus (VZV) genes that are expressed during active infection and during latency in the body. RNA transcripts corresponding to immediate-early and early VZV genes have been detected in human trigeminal ganglia using in situ hybridization and Northern analysis. At present, we mapping transcripts from these VZV genes and assaying their ability to regulate expression of other VZV genes by transient expression assays in vitro. VZV genes that are expressed during active infection and regulate viral gene expression are being studied. The transcriptional activation or repression domains of two of these regulatory proteins are being mapped. Cell lines have been constructed that stably express several of these VZV proteins and we are analyzing the effect of these proteins during infection of the cells with wild-type VZV or herpes simplex virus mutants. In addition cell lines are being constructed that secrete VZV glycoproteins which will be useful for evaluating the immune response to VZV and may be useful for generating subunit vaccines. Finally, we are constructing VZV mutants which are deleted for several of these regulatory genes or for genes encoding viral glycoproteins. Analysis of these viral mutants in cell culture and in animal models should provide further information on the role of individual VZV genes in active infection and during latency.

水痘-带状疱疹病毒引起水痘原发感染， 在病毒潜伏期的重新激活过程中。 该项目的目标是 鉴定和确定水痘带状疱疹病毒（VZV）基因的功能 在活跃感染和潜伏感染期间表达。 对应于即刻早期和早期VZV基因的RNA转录物具有 使用原位杂交在人三叉神经节中检测到， 北方分析。 目前，我们绘制了这些VZV的转录本 基因并测定它们调节其它VZV基因表达的能力 通过体外瞬时表达测定。 表达的VZV基因 在活跃的感染和调节病毒的基因表达正在 研究了 转录激活或抑制结构域的两个 这些调节蛋白正在被绘制。 细胞系已 构建了稳定表达这些VZV蛋白中的几种， 分析这些蛋白质在感染细胞期间的作用， 野生型VZV或单纯疱疹病毒突变体。 此外，细胞系是 构建分泌VZV糖蛋白的病毒载体， 评估对VZV的免疫应答，并可能有助于产生 亚单位疫苗 最后，我们正在构建VZV突变体， 这些调控基因中的几个或编码病毒的基因缺失 糖蛋白 这些病毒突变体在细胞培养物中的分析和在 动物模型应提供关于个体作用的进一步信息， 活动性感染和潜伏期的VZV基因。