HIV INFECTION OF NEURAL TISSUE--AN ORGANOTYPIC MODEL

人胎儿中枢神经系统器官型培养 组织将被用来检验这样的假设：人类 免疫缺陷病毒(HIV)可感染神经组织 怀孕了。这种感染可能解释了神经学上 一些患有先天性艾滋病毒的儿童出现功能障碍- 血清阳性，获得性免疫缺陷综合征(艾滋病)，或 艾滋病相关综合征(ARC)。试验性策略将 重点关注从择期妊娠中获得的胎儿中枢神经系统组织 终止艾滋病毒血清阴性的女性，艾滋病毒将成为 添加，以及来自HIV血清阳性或ARC或 艾滋病。HIV在器质性中枢神经系统中诱导病理的能力 培养物将通过显微镜和免疫细胞化学进行评估。 与核酸和蛋白质生物化学相结合。 具体来说，艾滋病毒感染不同神经细胞的能力 类型及其在单元格中的位置将由 病毒颗粒和免疫电子的电子显微镜 HIV特异性蛋白的显微镜染色。由于艾滋病毒是一种 可合并逆转录病毒及其基因组或部分基因组 转化宿主细胞DNA、Southern Blot分析和原位核 酸杂交将被用来检验这一点。一个 HIV诱导的神经病理的组成部分可能涉及改变 因此，在正常细胞类型的特定蛋白中，Western Blot 分析将被用来检查蛋白质可能的变化 差异化的合成与翻译后修饰 记号笔。为了确定新陈代谢的变化，额外的 研究将集中在感染组织中的酶动力学。 使用HIV感染者的流产培养物进行的类似实验 女性可能决定经胎盘胎儿感染的动力学 以及由此产生的神经病理学。这些实验将增强 对艾滋病毒感染的机制的理解 干扰正常的中枢神经系统组织发育。除了……之外 确定：(1)HIV是否可以感染神经细胞；(2)哪些细胞 被感染；以及，(3)细胞结构和 功能可能是由感染引起的。这些环境可能 定义T4分子以外的HIV受体。这样的洞察力 可允许设计改进的预防性或治疗性 与艾滋病毒感染作斗争的方案。

Organotypic cultures of human fetal central nervous system (CNS) tissue will be used to test the hypothesis that human immunodeficiency virus (HIV) can infect neural tissue during gestation. Such an infection might account for the neurologic dysfunction seen in some children with congenital HIV- seropositivity, acquired immunodeficiency syndrome (AIDS), or AIDS-related complex (ARC). The experimental strategies will focus on fetal CNS tissue obtained from elective pregnancy terminations of HIV-seronegative females, to which HIV will be added, and from females who are HIV-seropositive or have ARC or AIDS. The ability of HIV to induce pathology in organotypic CNS cultures will be assessed by microscopy and immunocytochemistry in conjunction with nucleic acid and protein biochemistry. Specifically, the ability of HIV to infect different neural cell types and its location within cells will be determined by electron microscopy for viral particles and immunoelectron microscopic staining for HIV-specific proteins. Since HIV is a retrovirus and its genome, or parts thereof, may be incorporated into host cell DNA, Southern Blot analysis and in situ nucleic acid hybridization will be used to examine this point. A component of HIV-induced neuropathology may involve alterations in normal cell-type specific proteins, therefore, Western Blot analyses will be used to examine possible changes in protein synthesis and post-translational modifications of differentiation markers. To determine alterations in metabolism, additional studies will focus on enzyme kinetics in infected tissue. Similar experiments using abortus cultures from HIV-infected females may define the kinetics of transplacental fetal infection and the resultant neuropathology. These experiments will enhance the understanding of the mechanisms by which HIV infection may interfere with normal CNS tissue development. In addition to determining: (1) if HIV can infect neural cells; (2) which cells are infected; and, (3) what perturbations of cell structure and function may result from infection. Those environments may define HIV receptors other than the T4 molecule. Such insights may permit the design of improved preventative or therapeutic protocols for combatting HIV infection.