MOLECULAR EPIDEMIOLOGY AND BIOLOGICAL DETERMINANTS OF HTLV-1

人T细胞白血病/嗜淋巴病毒I型(HTLV-I)与人类免疫缺陷病毒的研究 猴T细胞白血病病毒I型分子进化接近 完成了。几种亚洲猴源STLV-I的进一步分析 侏儒黑猩猩(它们比泛黑猩猩更接近人类)将 被执行。对HTLV-I兔模型的研究已经从 疫苗的致病机理，因为1)大鼠和小鼠已被确定为 成为HTLV-I更经济的模式，以及2)部分成功 NYVAC/ALVAC疫苗用于预防人类免疫缺陷病毒 类型2挑战(见Z01CP05688-03)。主要强调的是 新发现的Px区蛋白p12(I)的功能作用 HTLV-I基因组，它与HTLV-I的基因和功能相关 牛乳头瘤病毒1型(BPV-1)E5癌蛋白。此外，这一小块 位于高尔基复合体中的蛋白质与居民结合 高尔基复合体的蛋白质，质子H+的16千道尔顿亚基 液泡型ATPase。越来越多的证据表明，一些病毒蛋白 (BPV的e5，脾病灶形成病毒的gp55)可能通过结合发挥作用 生长因子受体和模拟天然配体的功能。这个 P12(I)在HTLV-L转化人T细胞中的可能作用 通过测试其与α-链和β-链的结合进行研究 白介素2受体。P12与IL-2特异性结合 β链，但不是阿尔法链。我们目前正在绘制 参与这些相互作用的蛋白质结构域，并同时尝试 建立一种造血细胞转化试验。 该项目的第二部分涉及HTLV-I的开发 疫苗。NYVAC和ALVAC HTLV-I结构(背景信息请参见 用表达HTLV-I包膜的Z01CP05688-03)免疫 兔子。针对这些结构的免疫反应的测试 免疫动物的自然免疫应答平行分析 人类正在进行中。

The study of human T-cell leukemia/lymphotropic virus type I (HTLV-I) and simian T cell leukemia virus type I (STLV-I) molecular evolution is near completion. Further analysis of STLV-I from a few Asian monkey species and pygmy chimpanzees (which are closer to humans than Pan Troglodytes) will be performed. Studies of HTLV-I rabbit models have shifted from pathogenesis to vaccine because 1) rats and mice have been determined to be a more economical model for HTLV-I, and 2) partial success of NYVAC/ALVAC vaccine for protection against human immunodeficiency virus type 2 challenge (see Z01CP05688-03). Major emphasis has been on the functional role of a newly identified protein, p12(I), from the pX region of the HTLV-I genome, 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-l transformation of human T-cells has been investigated by testing its binding to the alpha- and beta-chains of the interleukin 2 (IL-2) receptor. The p12 binds specifically to the IL-2 beta-chain but not to the alpha-chain. We are presently mapping the protein domains involved in these interactions and in parallel trying to develop a transformation assay in hematopoietic cells. The second part of this project involves the development of an HTLV-I vaccine. NYVAC and ALVAC HTLV-I constructs (for background information see Z01CP05688-03) expressing the HTLV-I envelope were used to immunize rabbits. Testing of the immunoresponse against these constructs in the immunized animals with parallel analysis on the natural immunoresponse in humans is ongoing.