TRANSCRIPTIONAL CONTROL OF BOVINE LEUKEMIA VIRUS

牛白血病病毒的转录控制

• 批准号: 2281084
• 负责人: PATRICIA J BROOKS
• 金额: $ 5.16万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2281084
• 关键词: DNA binding protein; DNA footprinting; chimeric proteins; cow; disease /disorder model; gene induction /repression; genetic mapping; genetic promoter element; leukemia virus; leukocyte activation /transformation; lymphocyte proliferation; protein kinase A; protein kinase C; provirus; transcription factor; virus infection mechanism; virus related neoplasm /cancer

The structural, functional and biological similarities of bovine leukemia virus (BLV) to human T cell leukemia viruses (HTLV) make BLV in cattle an excellent model to study oncogenic retroviral infections in humans. The long term objectives of this proposal are to define the relationship between the regulation of BLV transcriptional activation, and the activation and proliferation of B lymphocytes, the primary host cell target of BLV. The specific aims designed to accomplish these objectives in Phase I of the SERCA proposal are: 1. Characterize the interactions between BLV and cellular nuclear binding proteins and map the DNA-protein binding sites in the BLV provirus. The binding of putative nuclear transcription factors to the BLV LTR will be mapped using DNase I footprinting. 2. Identify and characterize transcriptional factors specifically associated with B cell activation that bind to the BLV promoter. Transcriptional factors from resting and activated bovine lymphocytes will be identified, and analyzed using the BLV LTR map. 3. Determine the role of the intracellular second messengers PKC and PKA in induction of BLV transcription. PKC and PKA inhibitors and activators will be used to define the roles of cellular PKC and PKA in BLV transcriptional activation. The last specific aim will be accomplished during Phase II of the SERCA proposal: 4. Determine the effects of BLV Tax on the nuclear binding protein's that interact with the BLV promoter. A Tax fusion protein will be developed to study Tax effects on BLV and B cell activation. These studies will provide new insights into the pathogenesis of oncogenic retroviruses, and will provide an excellent framework for training the candidate in molecular biological research.

牛白血病的结构，功能和生物学相似性 对人T细胞白血病病毒（HTLV）的病毒（BLV）使牛的BLV成为 研究人类致癌性逆转录病毒感染的出色模型。这 该提案的长期目标是定义关系 在BLV转录激活的调节和 B淋巴细胞的激活和增殖，主要宿主细胞 BLV的目标。旨在实现这些目标的具体目标 在SERCA提案的第一阶段中是： 1。表征BLV与细胞核结合之间的相互作用 蛋白质并绘制BLV病毒中的DNA-蛋白结合位点。 这 假定的核转录因子与BLV LTR的结合将是 使用DNase I足迹映射。 2。识别和表征转录因子 与与BLV启动子结合的B细胞激活相关。 静息和活化的牛淋巴细胞的转录因子将 可以识别并使用BLV LTR映射进行分析。 3。确定细胞内第二使者PKC和PKA的作用 在诱导BLV转录中。 PKC和PKA抑制剂和激活剂 将用于定义BLV中细胞PKC和PKA的作用 转录激活。 最后一个特定目标将在SERCA的第二阶段完成 提议： 4。确定BLV税对核结合蛋白的影响 与BLV启动子相互作用。税收融合蛋白将开发 研究税对BLV和B细胞激活的影响。这些研究将提供 对致癌病毒的发病机理的新见解，并将 为训练分子训练的框架提供了一个绝佳的框架 生物学研究。