HIV-1 INFECTION IN FETAL BRAIN CELL CULTURES AND PEDIATRIC AIDS BRAIN TISSUE

为了研究HIV-I分离株对神经系统的嗜性，我们 在来自以下来源的培养物中启动各种HIV-1菌株的感染 人类胎儿大脑病毒吸附后几天， 星形胶质细胞培养，测定病毒抗原。25个分离株中有7个 来自CSF或血液的病毒能够感染人类 星形胶质细胞从这些分离物中克隆了V3区编码序列 并确定核苷酸序列。没有证据表明 与感染了病毒的分离株相比， 星形胶质细胞然而，大多数感染性分离株是 合胞体诱导表型，亲淋巴细胞的特征 HIV- 1菌株。对这些分离株的进一步分子研究是 正在进行中用于这些实验的星形胶质细胞也不表达 α或β趋化因子受体。 我们还确定HIV-1反式激活蛋白达特能够 增加两种细胞蛋白质的活性。无论是转录 NF-κ B和细胞蛋白激酶PKC的表达水平高于对照组。 当星形胶质细胞用可溶性达特处理时，活性。的能力 调节细胞功能的HIV-1因子可能有助于解释 脑组织中的神经系统功能障碍， 活跃的病毒繁殖。我们还发现， β-趋化因子MCP-1的合成和释放， 艾滋病痴呆患者的发病率升高这些实验 旨在研究HIV-1感染在大脑中的机制。的 星形胶质细胞在大脑中作为HIV-1储存库的作用正在被 使用体外感染模式进行研究。

To investigate the tropism of HIV-I isolates for the nervous system, we initiated infection of various HIV-1 strains in cultures derived from human fetal brain. Following several days after virus adsorption on astrocyte cultures, viral antigen was measured. Seven of 25 isolates that were tested, derived from either CSF or blood, were able to infect human astrocytes. The V3 region coding sequences from these isolates were cloned and the nucleotide sequences determined. There was no evidence for unique sequences in this binding region compared to isolates that did infect astrocytes. However, the majority of the infectious isolates were syncytial inducing phenotype, characteristic of the lymphocytotropic strain of HIV- 1. Further molecular studies of these isolates are underway. Also the astrocytes used for these experiments did not express the alpha or beta chemokine receptor. We also determined that the HIV-1 transactivating protein, tat, is able to increase the activity of two cellular proteins. Both the transcription factor, NF-kB and the cellular protein kinase, PKC, demonstrated higher activity when astrocytes were treated with soluble tat. The ability of HIV-1 factors to regulate cellular functions may help explain the dysfunction of the nervous system in the brain tissue with little evidence of active virus multiplication. Also we found that HIV-1 that up regulates the synthesis and release of the beta-chemokine MCP-1 which is also found in elevated levels of AIDS patients with dementia. These experiments are designed to investigate the mechanism of HIV-1 infection in the brain. The role of the astrocyte as a reservoir of HIV-1 in the brain is being investigated using the in vitro mode of infection.