HIV XENOTRANSPLANTED NUDE MOUSE--ANTIVIRAL ASSAY MODEL

人类免疫缺陷病毒(HIV)是艾滋病的病原体。 到目前为止，只有两种FDA批准的药物可以直接提供 对这种病毒的抗病毒活性以及毒性和新出现的 阻力限制了它们的广泛应用。为了新的和 有效的抗艾滋病毒药物进入人体临床试验，小动物 需要模型来展示体内的活性。由于艾滋病毒是一种 独一无二的人类病毒，需要新的方法来引入这种病毒 变成了啮齿动物的宿主。其中一种方法是通过异种移植 人类艾滋病毒允许细胞进入亚致死剂量照射的无菌小鼠。这个 该提案的P.I.此前曾证明CEM细胞系 感染了HIV III-B毒株的人可以重现 使用这一新方法检测高水平的p24抗原血症。使用 期待将这一模式扩展为完全接受和有效的 HIV感染小动物模型的疗效评价 药物化合物，这项提案的总体目标是 继续完善这一模式。这将通过扩展来实现 移植方面包括各种不同的艾滋病毒允许细胞 表型；通过扩大HIV毒株(包括对AZT耐药和 主要)能够在此系统内复制，并通过引入 其他公认的测量病毒感染性的方法(即FAC 分析)。这一补充信息将为 设计药物治疗确定所需的实验 动物模型系统。

The Human immunodeficiency virus (HIV) is the etiological agent of AIDS. To date there are only two FDA approved drugs which provide direct antiviral activity against this virus, and both toxicities and emerging resistance limit their widespread utility. In order for new and efficacious anti-HIV agent to enter human clinical trials, small animal models are required to demonstrate in vivo activity. Since HIV is a uniquely human virus, novel means are required to introduce this virus into rodent hosts. One such means is through the xenotransplantation of human HIV permissive cells into sublethally irradiated athymic mice. The P.I. of this proposal has previously demonstrated that the CEM cell line infected with the III-B strain of the HIV can reproducibly demonstrate high levels of p24 antigenemia using this novel approach. With anticipation of expanding this model into a fully accepted and valid small animal model of HIV infection for efficacy evaluation of pharmaceutical compounds, it is the overall objective of this proposal to continue to refine this model. This will be accomplished be expanding the transplantation aspect to include HIV permissive cells of various phenotypes; by expanding the HIV strains (including AZT resistant & primary) capable of replication within this system, and by introducing other well established means of measuring viral infectivity (i.e., FACS analysis). This additional information will provide a firm basis to design the experiments required for drug therapy determinations in this animal model system.