DEVELOP ANIMAL MODELS OF ACQUIRED IMMUNODEFICIENCY

我们从自然感染的猴T细胞淋巴组织中分离到一种病毒 健康的黑尾猴(Cercocebus Atys)，一种非洲猴子，有 使该病毒适应在H9细胞中的体外生长。这种新的病毒分离株 是STLV-III样的，因为与核心的血清学交叉反应 人T细胞嗜淋病病毒III型抗原及其存在 在电子显微镜下呈现典型的慢病毒形态。我们的类STLV-III 分离株暂定名为STLV-III(Mangaby)。 在初步发病机制研究中，4只恒河猴(Rh)和1只猕猴(Macaca Mulatta) 对非洲绿猴(Cercopithecus Atheiops)进行了免疫接种。 STLV-III(芒果)。在接受测试的2只恒河猴中，有2只患有持续性病毒血症和 随着逆转录病毒感染的临床迹象，T4/T8比率逆转 12周和22周(全身性淋巴结病和脾肿大) 分别接种后(Pi)。转化为STLV-III的AGM血清， 但不是病毒携带者，13周时临床上是健康的。 这项建议旨在开发STLV-III的模型 (芒果病)-通过1)接种幼猴来致病 对于病毒，2)病毒的克隆和测序，3)准备 抗STLV-III(芒果)核心区的单抗，以及4)使用 用单抗和分子探针定位病毒在体内的表达 感染淋巴、唾液和神经组织的免疫组织化学和 原位杂交。 这项工作的重要性在于STLV-III(芒果)的关系 对人类艾滋病的病原体HTLV-III/LAV。接种RH猴 患有STLV-III的人有时会发展成一种类似艾滋病的疾病。相比之下，非洲 自发感染STLV-III的猴子在临床上是正常的。这些 研究将提供有关STLV-III生物学的详细知识 在猴子身上感染，将检查人与猿类的亲缘关系 慢病毒，将有助于阐明人类艾滋病发病机制中的问题， 尤其是在健康携带者方面。这种类型的研究 需要一个由临床医生、病理学家、分子医生组成的多学科小组 生物学家和病毒学家。这样的一个小组已经在 加州灵长类动物研究中心，并在 灵长类D型逆转录病毒感染的发病机制。

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.