EXPERIMENTAL TRANSMISSION OF HTLV I TO NON HUMAN PRIMATE

本合作项目建立了HTLV-I的动物模型 非人灵长类动物中与原发性HTLV-I病毒相关的疾病 分离自HTLV-I相关热带人类患者 痉挛性轻瘫（TSP）。 三只接种恒河猴中的两只 被感染并显示出疾病的迹象 1只动物出现 与原始患者的结果相同，肌肉 萎缩，多发性肌炎，关节炎，（手稿出版）。 的 第二只动物双重感染SIV并出现体征 提示在存在以下物质的情况下阴燃HTLV-I诱导的白血病 SIV免疫缺陷病。 五个额外的HTLV-I中的四个 接种动物无症状，但显示出持续性 HTLV-I PCR感染和淋巴细胞增多。 第五种动物 是培养和PCR阴性，伴有强烈的体液 反应，如通过蛋白质印迹分析测定的。 这些结果 提示免疫应答在控制HTLV-I中是重要 猕猴模型中的病毒表达。 我们想要定义免疫 这种控制机制。 我们现在已经扩展了我们的特征 细胞毒性细胞介导的免疫反应。 在 与Larry Wilson博士合作，自体转化B细胞 从每只动物中产生品系， 冷冻保存。 我们还获得了几个HTLV-I基因特异性- 牛痘病毒构建体。 这两种试剂现在可以 用于表征细胞毒性T细胞的存在和性质 在体内HTLV-I的对照中的淋巴细胞。 基金基础补助金， 风险研究出版物Beilke M.A.，Traina-Dorge VL，英格兰 JD，Blanchard J（1996）多发性肌炎，关节炎和葡萄膜炎， 实验性感染HTLV-I的猕猴 阿尔斯。 & Rheum. 39（4）：610-615。

This collaborative project established an animal model of HTLV-I associated disease in nonhuman primates with a primary HTLV-I viral isolate, derived from a human patient with HTLV-I associated tropical spastic paraparesis (TSP). Two of three inoculated rhesus macaques became infected and showed signs of disease. One animal presented with a findings identical to that in the original patient, with muscle atrophy, polymyositis, and arthritis, (manuscript published). The second animal was dually infected with SIV and developed signs suggestive of smoldering HTLV-I induced leukemia in the presence of SIV immunodeficiency disease. Four of five additional HTLV-I inoculated animals are asymptomatic but show evidence of persistent infection by HTLV-I PCR and increased lymphocytosis. The fifth animal is culture and PCR negative with an associated strong humoral response, as determined by western blot analysis. These results suggest that immune responses are important in controlling HTLV-I virus expression in the macaque model. We want to define the immune mechanism of this control. We have now extended our characterization of immune responses to that of cytotoxic cell mediated response. In collaboration with Dr. Larry Wilson, autologous transformed B cell lines from each animal were generated and are now stably cryopreserved. We have also obtained several HTLV-I gene specific - vaccinia virus constructs. These two reagents are now ready to be used to characterize the presence and nature of cytotoxic T lymphocytes in the control of HTLV-I in vivo. FUNDING Base Grant, Venture Research PUBLICATIONS Beilke M.A., Traina-Dorge VL, England JD, Blanchard J (1996) Polymyositis, Arthritis, and Uveitis in a macaque experimentally infected with HTLV-I. Arth. & Rheum. 39(4):610-615.