INTERACTION OF EBV TRANSACTIVATORS WITH CELLULAR FACTORS

EBV 转录因子与细胞因子的相互作用

• 批准号: 6113448
• 负责人: DAVID E GUTSCH
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6113448
• 关键词: B lymphocyte; Epstein Barr virus; SCID mouse; cell cell interaction; cell cycle proteins; disease /disorder model; fatty acid binding protein; gene expression; genetic regulation; lymphoma; proliferating cell nuclear antigen; protooncogene; tissue /cell culture; viral carcinogenesis; virus antigen; virus genetics; virus infection mechanism; virus protein

The hypothesis driving this work is that Epstein-Barr virus (EBV) transactivators are essential for EBV-induced malignancies. The goal of our work is uncovering the mechanisms whereby these transactivators function. We study the complex regulation of Epstein-Barr virus nuclear antigen (EBNA) expression during EBV infection. EBNA proteins contribute to the immortalization of B lymphocytes, and thus may have a role in the genesis of EBV-associated lymphomas. Another project involves the EBV lytic cycle protein, Z, and the cellular proto-oncogene, c-myb. The Z protein is responsible for initiating the switch from EBV latency to lytic infection. We have discovered that c-Myb markedly enhances the ability of Z to activate viral gene expression. Thus we are determining the mechanism of synergy between Z and c-Myb. We are collaboratively studying the regulation of Z expression using a SCID mouse model of immunosuppression-associated lymphomagenesis.

推动这项工作的假设是，爱泼斯坦 - 巴尔病毒（EBV）反式激活因素对于EBV引起的恶性肿瘤至关重要。 我们工作的目的是揭示这些反式激活器起作用的机制。 我们研究了EBV感染过程中爱泼斯坦 - 巴尔病毒核抗原（EBNA）表达的复杂调节。 EBNA蛋白有助于B淋巴细胞的永生化，因此可能在与EBV相关的淋巴瘤的起源中起作用。 另一个项目涉及EBV裂解循环蛋白Z和细胞原始癌基因C-MYB。 Z蛋白负责启动从EBV潜伏期转变为裂解感染的转换。 我们发现C-MYB显着增强了Z激活病毒基因表达的能力。因此，我们确定Z和C-MYB之间协同作用的机理。 我们正在使用与免疫抑制相关的淋巴作用的SCID小鼠模型进行协作研究Z表达的调节。