HERPESVIRUS PERSISTENCE AND ONCOGENICITY

疱疹病毒的持久性和致癌性

• 批准号: 6452859
• 负责人: THOMAS E SHENK
• 金额: $ 4.25万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6452859
• 关键词: Herpesviridae; Herpesviridae disease

Changes in cellular biochemical pathways are fundamental to herpesvirus persistence and oncogenicity. We will employ new global approaches to identify viral genes that modulate cellular pathways and to identify the pathways that are altered, and then we will elucidate the mode of action of these altered pathways within the infected cell. Our approach will be comparative. The program will include the study of viruses in each of the three families of herpesviruses: alpha, herpes simplex type 1 virus and pseudorabies virus; beta, human cytomegalovirus; and gamma, Epstein- Barr virus and Kaposi sarcoma-associated herpes virus. Some herpes viruses contribute to human cancers (Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus), while others are not known to do so. Consequently, our program will compare tumor viruses with closely related non-tumor viruses. The long-term objective of the program is to better understand the mechanisms by which herpesviruses persist and contribute to oncogenesis in the infected host. We will search for additional viral genes that mediate persistence and oncogenicity, and we will study the mechanism of action of new genes that are identified. We also will identify cellular genes whose level of expression change after infection, and test the hypothesis that some of these altered cellular genes influence the outcome of the virus-host interaction, contributing to the persistence and/or oncogenicity of the viruses. The individual research projects are as follows. Project 1, Roizman. Comparative role of cellular functions in herpes simplex type 1 virus infection. Project 2, Enquist Comparative alpha-herpesvirus (herpes simplex type 1 virus and pseudorabies virus) infection of the nervous system. Project 3, Shenk: Viral and cell gene function in human cytomegalovirus replication and latency. Project 4, Moore: Viral and cellular gene regulation in Kaposi sarcoma-associated herpesvirus-associated tumors. Project 5, Kieff: Epstein-Barr virus and cell gene expression in latency and oncogenesis.

细胞生化途径的改变是疱疹病毒持续性和致癌性的基础。我们将采用新的全球方法来识别调节细胞通路的病毒基因，并识别被改变的通路，然后我们将阐明这些被改变的通路在感染细胞内的作用模式。我们的方法将是比较的。该计划将包括对三种疱疹病毒家族中的每一种病毒的研究：α、单纯疱疹1型病毒和伪狂犬病毒；β，人巨细胞病毒；和γ，爱泼斯坦-巴尔病毒和卡波西肉瘤相关疱疹病毒。一些疱疹病毒会导致人类癌症（爱泼斯坦-巴尔病毒和卡波西肉瘤相关疱疹病毒），而另一些则不知道会这样做。因此，我们的程序将比较肿瘤病毒与密切相关的非肿瘤病毒。该项目的长期目标是更好地了解疱疹病毒在感染宿主体内持续存在并促进肿瘤发生的机制。我们将寻找介导持久性和致癌性的其他病毒基因，并研究已确定的新基因的作用机制。我们还将鉴定感染后表达水平发生变化的细胞基因，并验证这些改变的细胞基因影响病毒-宿主相互作用的结果，有助于病毒的持久性和/或致癌性的假设。个人研究项目如下：项目1，罗伊兹曼。细胞功能在1型单纯疱疹病毒感染中的比较作用。项目2：神经系统的比较α -疱疹病毒（单纯疱疹1型病毒和伪狂犬病毒）感染。项目3，申克：人巨细胞病毒复制和潜伏期中的病毒和细胞基因功能。项目4，Moore：卡波西肉瘤相关疱疹病毒相关肿瘤的病毒和细胞基因调控。项目5，Kieff: Epstein-Barr病毒和细胞基因在潜伏和肿瘤发生中的表达。