PATHOGENESIS AND EVOLUTION OF HUMAN T CELL LEUKEMIA/LYMPHOTROPIC VIRUSES

人类 T 细胞白血病/淋巴细胞病毒的发病机制和进化

• 批准号: 3752708
• 负责人: G FRANCHINI
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3752708
• 关键词: Cercopithecidae; T lymphocyte; biochemical evolution; cell transformation; cytokine receptors; genetic mapping; growth factor receptors; human T cell lymphotropic virus type 1; human tissue; interleukin 2; ligands; molecular pathology; protein structure function; receptor binding; simian virus; virus genetics; virus protein

Part of the study of human T-cell leukemia/lymphotropic virus type 1 (HTLV-I) and simian T-cell leukemia virus type 1 (STLV-I) molecular evolution has been completed. Further analysis of STLV-I from Asian monkey species and pygmy chimpanzees has revealed the presence of a novel virus which is related to HTLV-I and HTLV-II. This virus has been isolated and its genetic characterization is in progress. Major emphasis has been on the functional role of the HTLV-I p12 protein, which is correlated genetically and functionally to the bovine papillomavirus 1 (BPV-1) E5 oncoprotein. Further, this small protein, which is located in the golgi complex, binds to a resident protein of the golgi complex, the 16 kilodalton subunit of the proton H+ vacuolar ATPase. Increasing evidence suggests that some viral proteins (E5 of BPV, gp55 of spleen focus forming virus) might function by binding to growth factor receptors and mimic natural ligand function. The possible role of p12(I) in HTLV-I transformation of human T-cells has been investigated by testing its binding to the alpha, beta and gamma chains of the interleukin 2 receptor (IL-2R). The p12 binds specifically to the IL-2 beta and gamma but not to the alpha chains. Mapping of the binding domain of the IL-2 beta chains has revealed that the p12 protein binds to the acidic rich region of the beta chains which also interacts with the p56(lck), a tyrosine kinase expressed mainly in T-cells. Moreover, the p12(I) protein binds to the cytoplasmic or transmembrane portions of the IL-2R gamma chain. Experiments to address the functional relevance of these findings are in progress.

人类T细胞白血病/嗜淋巴细胞病毒1型的部分研究 （HTLV-I）和猴T细胞白血病病毒1型（STLV-I）分子 进化已经完成。 亚洲人STLV-I的进一步分析 猴子和侏儒黑猩猩的研究揭示了一种新的 与HTLV-I和HTLV-II相关的病毒。 这种病毒已经 分离，其遗传特性鉴定正在进行中。 主要重点 一直在HTLV-I p12蛋白的功能作用，这是 与牛乳头瘤病毒1型在遗传和功能上相关 （BPV-1）E5癌蛋白。 此外，这种小蛋白， 在高尔基复合体中，结合高尔基复合体的驻留蛋白， 质子H+液泡ATP酶的16千道尔顿亚基。 增加 有证据表明，BPV的一些病毒蛋白（E5，脾脏gp 55） 病灶形成病毒）可能通过与生长因子受体结合发挥作用 并模仿天然配体功能。 p12（I）在HTLV-I中的可能作用 已经通过测试其对人T细胞的转化进行了研究。 与白细胞介素2受体的α、β和γ链结合 （IL-2R）。 p12特异性结合IL-2 β和γ，但不 连接到阿尔法链 IL-2 β结合结构域的定位 p12蛋白结合到富含酸性的区域， 在也与p56（lck）相互作用的β链中， 激酶主要在T细胞中表达。 此外，p12（I）蛋白结合 与IL-2 R γ链的胞质或跨膜部分连接。 解决这些发现的功能相关性的实验在 中求进工作总