HIV INFECTION OF NEURAL XENOGRAFT

人类免疫缺陷病毒1型(HIV-1)感染中枢神经系统 成人和儿童的系统。人们对艾滋病病毒感染知之甚少。 胎儿神经系统，或关于母亲HIV-1的间接影响 对发育中的胎儿大脑的感染。标记的寄主物种 慢病毒的特异性和病毒宿主细胞的重要性 相互作用表明，需要一个模型，在该模型中， 分化，胎儿神经组织可感染HIV-1和/或 暴露于潜在的有毒病毒或宿主衍生因子。我们有 开发了一种模型，在该模型中，人类中期妊娠的胎儿大脑或视网膜 成人眼前房内异种组织的生长 老鼠。这些异种移植物血管化，建立血脑屏障， 部分分化为神经胶质细胞和神经元细胞。我们建议 建立和优化感染人胎儿神经的条件 带有HIV-1病毒的组织。为了分析HIV-1感染的过程，我们将 应用聚合酶链式反应(PCR)结合免疫组织化学和 原位杂交技术。更多研究将使我们能够 确定哪些HIV-1病毒株能够感染人类胎儿 大脑，哪些细胞类型(神经外胚层或其他)被感染，自然 每种细胞类型(生产性、限制性或潜伏性)的感染情况，以及 HIV-1对发育的直接或间接的形态影响 神经系统。这个模型在评估疗效方面应该是有用的。 针对神经系统感染HIV-1的抗病毒药物。

Human immunodeficiency virus type 1 (HIV-1) infects the central nervous system of adults and children. Little is known about HIV-1 infection of the fetal nervous system, or about the indirect effects of maternal HIV-1 infection on the developing fetal brain. The marked host species specificity of lentiviruses and the importance of viral-host cell interactions suggest that a model is required in which intact, differentiating, fetal neural tissue can be infected by HIV-1 and/or exposed to potentially toxic viral or host derived factors. We have developed a model in which human second trimester fetal brain or retinal tissues are grown as xenografts in the anterior chamber of the eye in adult rats. These xenografts vascularize, establish a blood-brain-barrier, and partially differentiate into glial and neuronal elements. We propose to establish and optimize conditions for infecting these human fetal neural tissues with HIV-1. To analyze the course of the HIV-1 infection, we will use polymerase chain reaction (PCR), coupled with immunohistochemical and in situ hybridization techniques. Additional studies will allow us to determine which viral strains of HIV-1 are capable of infecting human fetal brain, which cell types (neuroectodermal or other) are infected, the nature of infection in each cell type (productive, restricted, or latent), and the morphological effects, direct or indirect, of HIV-1 on the developing nervous system. This model should prove useful in assessing the efficacy of antiviral agents which target HIV-1 infection of the nervous system.