FUNCTIONAL ANALYSIS OF THE HUMAN T-LYMPHOTROPIC VIRUSES

人类嗜T淋巴细胞病毒的功能分析

• 批准号: 3199141
• 负责人: GILBERT JAY
• 金额: $ 13.47万
• 依托单位: AMERICAN NATIONAL RED CROSS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3199141
• 关键词: developmental genetics; embryo /fetus tissue /cell culture; flow cytometry; gene expression; genetic transcription; genetically modified animals; histochemistry /cytochemistry; human T cell lymphotropic virus type 1; human T cell lymphotropic virus type 2; human tissue; laboratory mouse; molecular cloning; molecular pathology; nucleic acid sequence; polymerase chain reaction; regulatory gene; reporter genes; single cell analysis; spastic paralysis; transcription factor; viral leukemogenesis; virulence; virus DNA; virus genetics

The long term goals of this proposal are to define the role of HTLV-1 like viruses in inducing human disease, including malignant lymphoid neoplasia and degenerative neurological disorders, and to derive transgenic mice carrying genes from these HTLV-like viruses to delineate the mechanisms of disease pathogenesis. This application is composed of four specific but interrelated aims: [1] to define using transgenic mice and at the single cell level the tissue-specificity of the prototype HTLV-1 long terminal repeat (LTR), either in the absence or presence of the HTLV-1 trans-activator (tax); [2] to determine using transgenic mice the differences between HTLV-2 and the prototype HTLV-1, both in terms of LTR specificity and role of the tax gene in inducing pathogenesis; [3) to clone using PCR amplification HTLV-like sequences directly from the involved tissues of patients with Tropical Spastic Paraparesis (TSP), and to compare their DNA sequences with the prototype HTLV-1; and [4) to ascertain using transgenic mice the functional significance of the base substitutions detected among the various HTLV-like sequences from TSP patients, and to determine whether such substitutions are responsible for altering disease phenotypes.

这项提案的长期目标是定义HTLV-1这样的角色 病毒导致人类疾病，包括恶性淋巴肿瘤 和退行性神经疾病，并产生转基因小鼠 携带这些HTLV样病毒的基因来描述 疾病发病机制。 本申请由四个具体但相互关联的目标组成： [1]使用转基因小鼠并在单细胞水平上定义 HTLV-1原型长末端重复序列的组织特异性， 在HTLV-1反式激活剂不存在或存在的情况下(TAX)； [2]利用转基因小鼠确定HTLV-2和HTLV-2的差异 HTLV-1原型，既有LTR的特殊性，也有税务的作用 致病基因； [3]直接用聚合酶链式反应扩增克隆HTLV类序列 热带痉挛性瘫痪(TSP)患者的受累组织，以及 将它们的DNA序列与HTLV-1原型进行比较；以及 [4]利用转基因小鼠确定该基因的功能意义 从TSP中检测到的各种HTLV样序列中的碱基替换 患者，并确定这种替代是否对 改变疾病表型。