EXPRESSION--SYNTHETIC DNA SEQUENCES/HTLV-I ENV PROTEN

人I细胞白血病病毒I(HTLV-I)是一种转化型逆转录病毒 与成人T细胞白血病/淋巴瘤和 热带痉挛麻痹。HILV-I血清阳性人数 美国的献血者正变得惊人地高，这引发了人们的担忧 关于可输血产品的污染。发展 一种高灵敏度和高特异性的血液筛查试验 血清中的HTLV-I抗体受到限量的阻碍 某些病毒蛋白，包括免疫原性最强的蛋白， 信封。拟议的第一阶段研究概述了一项战略 表示选定部分以及整个信封 使用合成DNA编码序列的蛋白质。这是意料之中的 这种方法将使这些多肽得以表达 在大肠杆菌中含量很高。表达的多肽将是 对它们进行生化分析并评估其检测能力 人血清中抗HTL7-I抗体。在第二阶段，前景看好 候选包膜多肽将用于配置 酶联免疫分析法检测人群中HTLV-I抗体 人类血清。将评估环境影响评估的敏感性，并 用大量正常人和感染者血清的特异性 个人。预计将有一套互补的 重组的HTL7-I蛋白将被配置成一个高表达的 接触这种病毒的高质量血液筛查试验。

Human I-cell leukemia virus I (HTLV-I) is a transforming retrovirus etiologically associated with adult T-cell leukemia/lymphoma and troPical spastic ParaParesis. The number of HILV-I seropositive blood donors in the US is becoming alarmingly high raising concerns about contamination of transfusable blood products. Development of a highly-sensitive and highlyspecific blood-screening assay for HTLV-I antibodies in serum has been hindered by limiting quantities of certain viral proteins, including the most immunogenic protein, envelope. The proposed Phase I study outlines a strategy for expressing selected portions, as well as the entire envelope protein using synthetic DNA coding sequences. It is anticipated that this approach will allow these polypeptides to be expressed at high levels in E.coli. The expressed polypeptides will be analyzed biochemically and evaluated for their ability to detect antibodies to HTL7-I in human sera. In Phase II, promising candidate envelope polypeptides will be used to configure an enzyme-linked immunoassay (EIA) to detect antibodies to HTLV-I in human sera. The EIA will be evaluated for sensitivity and specificity using sera from a large number of normal and infected individuals. It is envisaged that a complementary set of recombinant-derived HTL7-I proteins will be configured into a high- quality blood-screening assay for exposure to this virus.