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。 对HIV-1感染的了解很少， 胎儿的神经系统，或关于母体HIV-1的间接影响 对发育中的胎儿大脑造成感染 标记的宿主种 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， 分化中，胎儿神经组织可以被HIV-1感染和/或 暴露于潜在毒性病毒或宿主衍生因子。 我们有 开发了一个模型，其中人类中期妊娠胎儿的大脑或视网膜 组织作为异种移植物生长在成人的眼前房中 大鼠 这些异种移植物血管化，建立血脑屏障， 部分分化成神经胶质和神经元成分。 我们建议 建立并优化感染这些人胎儿神经细胞条件 携带HIV-1的组织 为了分析HIV-1感染的过程，我们将 使用聚合酶链反应（PCR），再加上免疫组化和 原位杂交技术。 进一步的研究将使我们能够 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，性质 每种细胞类型（生产性、限制性或潜伏性）的感染，以及 HIV-1对发育中的 神经系统 这个模型应该证明是有用的， 针对神经系统HIV-1感染的抗病毒药物。

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.