DEVELOP ANIMAL MODELS OF ACQUIRED IMMUNODEFICIENCY

开发获得性免疫缺陷的动物模型

• 批准号: 3595461
• 负责人: PRESTON MARX
• 金额: $ 25.88万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-15 至 1991-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3595461
• 关键词: AIDS; Retroviridae; antiAIDS agent; antibody formation; antiviral agents; bacterial disease; cellular immunity; disease /disorder model; disease carrier state; drug metabolism; drug screening /evaluation; environmental stressor; host organism interaction; humoral immunity; immunochemistry; medical complication; model design /development; molecular cloning; monoclonal antibody; nucleic acid sequence; pathologic process; simian virus; viral vaccines; virus diseases; virus infection mechanism

We have isolated a simian T-cell lymphotropic virus from naturally infected healthy sooty mangabeys (Cercocebus atys), an African monkey, and have adapted this virus to in vitro growth in H9 cells. This new viral isolate is STLV-III-like because of serological cross-reactions with the core antigen of human T cell lymphotropic virus-III (HTLV-III) and the presence of typical lentiviral morphology by electron microscopy. Our STLV-III-like isolate is provisionally designated STLV-III (mangabey). In preliminary pathogenesis studies, 4 rhesus (Rh) (Macaca mulatta) and 1 African green monkey (AGM) (Cercopithecus aethiops) were inoculated with STLV-III (mangabey). Two of 2 rhesus tested have persistent viremia and T4/T8 ratio reversals along with clinical signs of retroviral infection (generalized lymphadenopathy and splenomegaly) at 12 and 22 weeks post-inoculation (pi) respectively. The AGM seroconverted for STLV-III, but is not viremic and is clinically healthy at 13 weeks pi. This proposal is directed toward developing a model for STLV-III (mangabey)-pathogenesis in monkeys by 1) inoculation of juvenile monkeys with the virus, 2) cloning and sequencing the virus, 3) preparing monoclonal antibodies to the core of STLV-III (mangabey), and 4) using monoclonal antibody and molecular probes to localize virus expression in infected lymphoid, salivary and neural tissues by immunohistochemistry and in situ hybridization. The importance of this work lies in the relationship of STLV-III (mangabey) to HTLV-III/LAV, the etiologic agent of human AIDS. Rh monkeys inoculated with STLV-III sometimes develop an AIDS-like disease. In contrast, African monkeys spontaneously infected with STLV-III are clinically normal. These studies will provide detailed knowledge of the biology of STLV-III infection in monkeys, will examine the relatedness of human and simian lentiviruses and will help illucidate questions in human AIDS pathogenesis, especially with respect to healthy carriers. This type of research requires a multi-disciplinary group of clinicians, pathologists, molecular biologists, and virologists. Such a group has been assembled at the California Primate Research Center and has established expertise in the pathogenesis of primate type D retroviral infections.

我们已经从自然感染的猴T细胞嗜淋巴细胞病毒中分离出了一种 健康的白眉猴（Cercocebus atys），一种非洲猴子， 使该病毒适应在H9细胞中的体外生长。 这种新的病毒分离物 是STLV-III样的，因为与核心的血清学交叉反应 人T细胞嗜淋巴细胞病毒-III（HTLV-III）的抗原和存在 慢病毒的典型形态。 我们的STLV-III型 分离株暂时命名为STLV-III（mangabey）。 在初步发病机制研究中，4只恒河猴（Rh）（Macaca mulatta）和1只 非洲绿色猴（AGM）（Cercopithecus aethiops）接种 STLV-III（mangabey）. 两个恒河猴测试有持续的病毒血症， T4/T8比值随着逆转录病毒感染的临床体征沿着逆转 第12周和第22周时（全身淋巴结病和脾肿大） 接种后（pi）。 AGM血清转化为STLV-III， 但在感染后13周时不是病毒血症且临床上健康。 本建议是针对发展一个模型STLV-III （mangabey）-通过1）接种幼龄猴在猴中的发病机制 用病毒，2）克隆和测序病毒，3）制备 针对STLV-III核心的单克隆抗体（mangabey），和4）使用 单克隆抗体和分子探针来定位病毒在 免疫组织化学法检测感染的淋巴、唾液和神经组织， 原位杂交 这项工作的重要性在于STLV-III（mangabey） HTLV-III/LAV，人类艾滋病的病原体。 Rh猴接种 患有STLV-III的人有时会患上类似艾滋病的疾病。 相反，非洲 自发感染STLV-III的猴子在临床上是正常的。 这些 研究将提供STLV-III生物学的详细知识 在猴子中的感染，将检查人类和猿类的相关性， 慢病毒，将有助于阐明人类艾滋病发病机制中的问题， 特别是对于健康的携带者。 这种类型的研究 需要一个多学科的临床医生，病理学家，分子 生物学家和病毒学家 这样一个团体已经聚集在 加州灵长类动物研究中心，并已在 灵长类D型逆转录病毒感染的发病机制。