MODELS OF AIDS DEMENTIA COMPLEX

中枢神经系统（CNS）中HIV-1感染的发病机制是 不确定 调节HIV-1产生的因素在艾滋病中的作用 大脑或实际上对神经细胞造成损害的药物仍然是 定义了 使用转基因小鼠技术，我们将解决几个 与体内HIV-1的神经发病机制相关的假设包括： 1.大脑中的炎症会激活HIV-1。 使用已建立的线路 在转基因小鼠中，β-半乳糖苷酶（β-gal）在 根据HIV-1长末端重复序列（LTR）的大脑方向，我们将 用脑刺伤和单纯疱疹病毒制造炎症 1型脑炎 β-半乳糖生产将比较处理和 未处理的小鼠。 2.肿瘤坏死因子-α（TNF-α）在体内分泌时具有神经毒性。 大脑 我们将产生转基因小鼠，其表达TNF-α， 脑特异性启动子，胶质细胞酸性蛋白， 蛋白（GFAP），对子代小鼠进行神经病理学评估，并比较 与HIV-1 CNS感染中所见的神经病理学相似。 3. HIV-1，反式激活蛋白（达特）是神经毒性时，分泌在 个脑袋 我们将创造两组转基因小鼠，它们在小鼠体内表达达特。 在GFAP和HIV-1 LTR的指导下， 对后代小鼠进行神经病理学检查，并与之进行神经病理学比较 在HIV-1 CBS感染中可见。 4. TNF-α和达特激活大脑中的HIV-1 LTR。 转基因小鼠 在大脑中表达TNF-α和达特的小鼠将与HIV-1 LTR- β-gal小鼠，携带两种转基因的后代将被评估， 与携带一种或两种β-半乳糖的同窝仔相比， 也不是转基因。

The pathogenesis of HIV-1 infection in the central nervous system (CNS) is uncertain. The role of factors which regulate HIV-1 production in the brain or which actually cause damage to neural cells remains to be defined. Using transgenic mouse technology we will address several hypotheses relevant to the neuropathogenesis of HIV-1 in vivo including: 1. Inflammation in the brain activates HIV-1. Using an established line of transgenic mice in which beta-galactosidase (beta-gal) is expressed in the brain under the direction of HIV-1 long terminal repeat (LTR), we will create inflammation with a cerebral stab wound and herpes simplex virus type 1 encephalitis. beta-gal production will be compared in treated and untreated mice. 2. Tumor necrosis factor-alpha (TNF-alpha) is neurotoxic when secreted in the brain. We will generate transgenic mice which express TNF-alpha under the direction of a brain specific promoter, glial fibrillary acidic protein (GFAP), evaluate offspring mice neuropathologically, and compare the neuropathology to that seen in HIV-1 CNS infection. 3. HIV-1, transactivating protein (tat) is neurotoxic when secreted in the brain. We will create two sets of transgenic mice which express tat in the brain under the direction of GFAP and HIV-1 LTR, evaluate the offspring mice neuropathologically, and compare the neuropathology to that seen in HIV-1 CBS infection. 4. TNF-alpha and tat activate HIV-1 LTR in the brain. Transgenic mice expressing TNF-alpha and tat in the brain will be bred with HIV-1 LTR- beta-gal mice, and offspring carrying both transgenes will be assessed for beta-gal production in comparison to littermates who carry either one or neither transgene.