TRANSCRIPTIONAL CONTROL OF BOVINE LEUKEMIA VIRUS

牛白血病病毒的转录控制

• 批准号: 2281083
• 负责人: PATRICIA J BROOKS
• 金额: $ 4.99万
• 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/2281083
• 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 病毒（BLV）到人类 T 细胞白血病病毒（HTLV）使牛体内的 BLV 研究人类致癌逆转录病毒感染的优秀模型。这 该提案的长期目标是定义这种关系 BLV 转录激活的调节与 B淋巴细胞（初级宿主细胞）的激活和增殖 BLV 的目标。为实现这些目标而设计的具体目标 SERCA 提案第一阶段的内容是： 1. 表征 BLV 与细胞核结合之间的相互作用 蛋白质并绘制 BLV 原病毒中 DNA-蛋白质结合位点的图谱。 这 假定的核转录因子与 BLV LTR 的结合将是 使用 DNase I 足迹法进行映射。 2. 特异性识别和表征转录因子 与结合 BLV 启动子的 B 细胞激活相关。 来自静息和活化牛淋巴细胞的转录因子将 使用 BLV LTR 图进行识别和分析。 3.确定细胞内第二信使PKC和PKA的作用 诱导 BLV 转录。 PKC 和 PKA 抑制剂和激活剂 将用于定义细胞 PKC 和 PKA 在 BLV 中的作用 转录激活。 最后一个具体目标将在 SERCA 第二阶段完成 提议： 4. 确定 BLV Tax 对核结合蛋白的影响 与 BLV 启动子相互作用。将开发 Tax 融合蛋白 研究税收对 BLV 和 B 细胞激活的影响。这些研究将提供 对致癌逆转录病毒发病机制的新见解，并将 为培训候选人提供一个优秀的分子分子框架 生物学研究。