Role of Agno Protein in JC Virus Life Cycle

Agno 蛋白在 JC 病毒生命周期中的作用

• 批准号: 6736960
• 负责人: MAHMUT SAFAK
• 金额: $ 28.6万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6736960
• 关键词: AIDS /HIV neuropathy; Polyomavirus hominis 2; central nervous system; clinical research; gene deletion mutation; gene expression; genetic mapping; genetic regulation; genetic transcription; human tissue; nervous system disorder; neural degeneration; oligodendroglia; phosphorylation; point mutation; progressive multifocal leukoencephalopathy; protein protein interaction; protein structure function; transcription factor; transfection; virus antigen; virus protein; virus replication

DESCRIPTION (provided by applicant): Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) resulting from the lytic infection of oligodendrocytes by the human polyomavirus, JC virus (PML was once considered a rare complication of middle-aged and elderly patients with lymphoprolifera diseases. In recent years, however, increasingly high incidence of PML in AIDS patients than those wit immunosuppressive disorders led us to believe that PML may also be regarded as a AIDS-associated disease. Lytic phase of JCV appears to be highly complex and remains elusive. A growing body of experimental evidence suggests that the regulation of JC viral gene expression and replication is not mediated solely by the presence absence of a particular transcription factor in a given cell. Rather delicate interactions among transcription or interactions between host and viral regulatory proteins appear to be important determining factors in respect. In support of this hypothesis, we have recently presented evidence of specific functional interactions between a cellular factor, YB-1, and JCV T-antigen and showed that both proteins play important roles in J expression. In addition, our most recent published and unpublished data indicate that JCV late Agno protein, antigen, also appears to have regulatory roles in both viral gene expression and DNA replication through interaction with viral and cellular proteins, notably with T-antigen and YB-1. Hence, here we propose investigate the molecular mechanisms involved in regulation of JCV by the functional interplay between T-antigen, Agno and YB-1. By employing molecular biology, genetics and virological approaches, we will i) perform thorough molecular virological studies to determine the role of Agno in regulation of JCV gene transcription and replication by examining its physical and functional interaction with T-antigen and YB- 1; ii) investigate the function importance of Agno viral lytic cycle by means of both ectopic expression of Agno early in infection mutational analysis and; iii) characterize the potential phosphorylation sites of Agno protein and investigate the role in JCV life cycle. The results from such comprehensive studies will provide valuable information underlying mechanisms involved in both JCV gene regulation and replication; and thereby the progression of JCV-induced CNS disease.

描述（由申请人提供）：进行性多灶性白质脑病 (PML)是中枢神经系统（CNS）的脱髓鞘疾病， 来自人多瘤病毒JC对少突胶质细胞的溶解性感染 病毒（PML曾被认为是中老年人的罕见并发症 淋巴组织增生性疾病患者。然而，近年来， 艾滋病患者PML发生率高于免疫抑制者 疾病使我们相信PML也可能被视为艾滋病相关疾病 疾病JCV的裂解相似乎是高度复杂的，仍然难以捉摸。一 越来越多的实验证据表明，JC病毒的调节 基因的表达和复制并不完全是由存在和不存在介导的。 特定的转录因子。相当微妙 转录之间的相互作用或宿主与病毒之间的相互作用 调节蛋白似乎是重要的决定因素。在 为了支持这一假设，我们最近提出了具体的证据， 细胞因子YB-1和JCV T抗原之间的功能性相互作用， 表明这两种蛋白在J表达中起重要作用。此外，本发明还提供了一种方法， 我们最近发表和未发表的数据表明，JCV晚期阿尼奥 蛋白质，抗原，似乎也有调节作用，在这两个病毒基因 通过与病毒和细胞的相互作用， 蛋白质，特别是与T抗原和YB-1。因此，在这里，我们建议调查 通过功能调节JCV的分子机制， T抗原、阿尼奥和YB-1之间相互作用。通过使用分子生物学， 遗传学和病毒学方法，我们将i）进行彻底的分子生物学研究， 病毒学研究以确定阿尼奥在JCV基因调控中的作用 转录和复制，通过检查其物理和功能 与T抗原和YB- 1的相互作用; ii）研究功能重要性 阿尼奥病毒裂解周期的早期异位表达， 感染突变分析; iii）表征潜在的 阿尼奥蛋白的磷酸化位点，并研究在JCV生命中的作用 周期这种全面研究的结果将提供有价值的 JCV基因调控和 复制;并由此导致JCV诱导的CNS疾病的进展。