MOLECULAR EPIDEMIOLOGY AND BIOLOGICAL DETERMINANTS OF HTLV-1

该项目的目的是研究人类嗜T淋巴细胞病毒I型 (HTLV-I)的起源和进化及其在热带疾病中的致病作用 痉挛性截瘫/HTLV-I相关性脊髓病(TSP/HAM)。为了研究 分析了HTLV-I的起源、进化和在世界范围内的传播 来自感染个体的体外样本的病毒序列，其 已知其起源、临床诊断和一般背景。使用这个 方法，我们能够发现一种新的HTLV-I变异体在 并正式证明HTLV-I是 通过奴隶贸易活动在新世界传播。我们延长了 我们对HTLV-I近亲(猴T细胞白血病)的遗传学研究 病毒)，这种病毒存在于自然感染的猴子体内。我们仍然是 不同来源TSP/Ham中HTLV-I致病作用的研究 角度：1)通过研究哪些病毒基因在猪瘟的细胞中表达 被感染的病人。例如，在这项研究中，我们发现了新的HTLV-I 剪接的信使核糖核酸；2)通过开发新的蛋白质 TSP/Ham的动物模型(先是兔子，然后可能是猴子) 使用患者的现场病毒分离株，而不是适应的培养 HTLV-I。

The aim of this project is to study the human T lymphotropic virus type-I (HTLV-I) origin and evolution, and its pathogenetic role in tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the origin, evolution and HTLV-I dissemination in the world, we analyzed viral sequences from ex vivo samples of infected individuals, whose origin, clinical diagnosis and general background were known. Using this approach, we were able to identify a novel HTLV-I variant in the southwestern Pacific Islands and formally prove that HTLV-I was disseminated in the New World through slave trade events. We extended our genetic studies to the close HTLV-I relatives (simian T cell leukemia virus) which are found in naturally infected monkeys. We are still investigating the pathogenetic role of HTLV-I in TSP/HAM from different angles: 1) by studying which viral genes are expressed in the cells of infected patients. For example, in this study we identify novel HTLV-I spliced messenger ribonucleic acids; and 2) novel proteins by developing an animal model (rabbits first and perhaps monkeys later) for TSP/HAM using field viral isolates from patients rather than culture adapted HTLV-I.