MOLECULAR EPIDEMIOLOGY AND BIOLOGICAL DETERMINANTS OF HTLV-1

该项目的目的是研究人类T淋巴细胞嗜酸病毒I型 (HTLV-I)的起源和进化及其在人类免疫缺陷病毒中的致病作用 HTLV-I相关性脊髓病/热带痉挛截瘫(HAM/TSP)。至 研究HTLV-I的起源、进化和在世界上的传播，我们 从感染者的体外样本中分析了病毒序列， 其起源、临床诊断和一般背景已知。vbl.使用 通过这种方法，我们能够识别出一种新的HTLV-I变异株 并正式证明HTLV-I是 通过奴隶贸易活动在新世界传播。我们计划 将我们的基因研究扩展到HTLV-I的近亲(猿猴T细胞 白血病病毒)，这种病毒存在于自然感染的猴子体内。我们是 HTLV-I在火腿/TSP中致病作用的研究 不同的角度：1)通过研究哪些病毒基因在 感染患者的细胞。例如，在这项研究中，我们确定了小说 HTLV-I剪接mRNAs；2)建立动物模型(首先是兔子和 也许是猴子)使用野生型病毒分离株进行火腿/TSP 患者而不是培养适应HTLV-I；以及3)测试 特殊抗病毒疗法(反义寡核苷酸或逆转录病毒 携带分子诱饵的载体)体内外(兔) 靶向特定的HTLV-I基因。

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 HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To study the origin, evolution and HTLV-I dissemination in the world, we analyzed viral sequence from ex vivo samples of infected individuals, whose origin, clinical diagnosis and general background was 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 plan to extend our genetic studies to the close HTLV-I relatives (simian T cell leukemia virus) which are found in naturally infected monkeys. We are investigating the pathogenetic role of HTLV-I in HAM/TSP from three 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 mRNAs; 2) by developing an animal model (rabbits first and perhaps monkeys later) for HAM/TSP using field viral isolates from patients rather than culture adapted HTLV-I; and 3) testing the effect of special antiviral therapy (antisense oligonucleotides or retroviral vector carrying molecular decoys) in vitro and in vivo (in rabbits) targeting specific HTLV-I genes.