PATHOGENESIS AND EVOLUTION OF HUMAN T CELL LEUKEMIA/LYMPHOTROPIC VIRUSES

人类T细胞白血病/嗜淋巴细胞病毒1型研究的一部分 (HTLV-I)和猴T细胞白血病病毒1型(STLV-I)分子 进化已经完成。亚洲地区STLV-I的进一步分析 猴子物种和侏儒黑猩猩揭示了一种新的存在 与HTLV-I和HTLV-II相关的病毒。这种病毒已经被 该病毒已被分离，其基因特征正在研究中。主要侧重点 一直在研究HTLV-I p12蛋白的功能作用，这是 与牛乳头瘤病毒1型在基因和功能上的相关性 (BPV-1)E5癌蛋白。此外，这种小蛋白质，它位于 在高尔基复合体中，与高尔基复合体的驻留蛋白结合， 质子H+液泡型ATPase的16千道尔顿亚基。渐增 有证据表明，一些病毒蛋白(BPV的E5，脾的gp55 病灶形成病毒)可能通过与生长因子受体结合而发挥作用 并模仿天然配基的功能。P12(I)在HTLV-I中的可能作用 人类T细胞的转化已被研究通过检测其 与白细胞介素2受体的α、β和伽马链结合 (IL-2R)。P12与IL-2β和γ特异性结合，但不与之结合 到阿尔法链。白介素2β结合区的定位 Chains揭示了p12蛋白与酸性富集区的结合。 在与p56(Lck)相互作用的β链中，有一种酪氨酸 蛋白激酶主要在T细胞中表达。此外，p12(I)蛋白结合 到IL-2R伽马链的细胞质或跨膜部分。 关于这些发现的功能相关性的实验发表在 进步。

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.