Herpesviral Oncogenesis, Latency and Reactivation

疱疹病毒肿瘤发生、潜伏期和再激活

• 批准号: 7908032
• 负责人: NANCY JOAN RAAB-TRAUB
• 金额: $ 24.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7908032
• 关键词: Herpesviral; Oncogenesis; Latency; Reactivation

DESCRIPTION (provided by applicant): The Virology Program Project continues its focus on the identification of interactions between viral and cellular proteins in herpesvirus infection and the effects of viral infection on cellular growth control. The program project includes basic studies of protein/DNA interactions on origins of replication, viral regulation of expression, viral effects on cell function, and the effects of tumor suppressor loss on viral tumorigenesis. Dr. Jack Griffith will continue his studies of herpes simplex virus (HSV) replication proteins, characterizing the replication complex on ori-S and the role of recombination proteins in initiation of replication. Dr. Shannon Kenney will pursue her studies of the Epstein Barr virus (EBV) ori-lyt and the role of BMRF1, the EBV polymerase processivity factor, and the Z and R transactivators and their effects on ori-lyt methylation and cellular repair mechanism. Dr. Joseph Pagano will continue his studies of Type III latency. He will analyze cell cycle effects and the role of the beta-catenin/TCF pathway in regulation of Type III latency. Dr. Eng Shang Huang has shown that HCMV gB binds to and activates the epidermal growth factor receptor. During this funding period, he will further characterize this interaction and, identify the domains of gB and EGFR that interact and develop a bacmid system to produce gB mutants in the context of the virus. Dr. Nancy Raab-Traub, Principal Investigator, will continue her studies of LMP1-induced transformation in transgenic mice and in rodent fibroblasts. She will further characterize the synergistic effects of loss of p16Ink4/p19ARF and LMP1 expression on lymphomagenesis and analyze transgenic mice that express both LMP1 and LMP2 in lymphocytes and epithelial cells. Overall, the Program Project will-continue to dissect the viral/cellular molecular interactions that occur during viral infection and determine how specific molecular events contribute to herpesvirus pathogenesis.

描述(由申请人提供)：病毒学计划项目继续专注于确定疱疹病毒感染中病毒和细胞蛋白之间的相互作用，以及病毒感染对细胞生长控制的影响。该计划项目包括关于复制起源的蛋白质/DNA相互作用的基础研究，病毒表达的调节，病毒对细胞功能的影响，以及肿瘤抑制基因缺失对病毒肿瘤形成的影响。Jack Griffith博士将继续他对单纯疱疹病毒复制蛋白的研究，表征Ori-S上的复制复合体以及重组蛋白在复制启动中的作用。Shannon Kenney博士将继续研究Epstein Barr病毒(EBV)Ori-lyt和BMRF1的作用，EBV聚合酶加工因子，Z和R反式激活因子及其对Ori-lyt甲基化和细胞修复机制的影响。约瑟夫·帕加诺博士将继续他对III型潜伏期的研究。他将分析细胞周期效应和β-连环蛋白/TCF通路在调节III型潜伏期中的作用。黄英尚博士已经证明，人巨细胞病毒gb能结合并激活表皮生长因子受体。在这一资助期间，他将进一步描述这种相互作用的特征，并确定GB和EGFR相互作用的区域，并开发一个杆状病毒系统，在病毒的背景下产生GB突变。首席研究员Nancy Raab-Traub博士将继续她对LMP1在转基因小鼠和啮齿动物成纤维细胞中诱导转化的研究。她将进一步表征p16Ink4/p19ARF和LMP1表达缺失对淋巴癌发生的协同作用，并分析在淋巴细胞和上皮细胞中同时表达LMP1和LMP2的转基因小鼠。总体而言，该计划项目将继续剖析病毒感染期间发生的病毒/细胞分子相互作用，并确定特定的分子事件如何有助于疱疹病毒的发病。