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趋向性，我们 不同HIV-1毒株在来源于 人类胎儿的大脑。在病毒吸附后几天 星形胶质细胞培养，检测病毒抗原。25个分离株中的7个 经检测，从脑脊液或血液中提取的病毒能够感染人类 星形胶质细胞。克隆了这些分离株的V3区编码序列 以及确定的核苷酸序列。没有证据表明这是唯一的 该结合区的序列与感染该病毒的分离物的比较 星形胶质细胞。然而，大多数具有感染性的分离株是 合胞诱导表型，淋巴细胞趋化的特征 这些分离株的进一步分子研究是 正在进行中。此外，用于这些实验的星形胶质细胞也没有表达 α或β趋化因子受体。 我们还确定了HIV-1反式激活蛋白TAT能够 提高两种细胞蛋白质的活性。这两份抄本 核因子-kB和细胞蛋白激酶C表现出较高的水平 可溶性TAT处理星形胶质细胞时的活性。的能力 HIV-1调节细胞功能的因子可能有助于解释 脑组织中的神经系统功能障碍，几乎没有证据 活跃的病毒繁殖。我们还发现HIV-1上调了 还发现了β-趋化因子MCP-1的合成和释放 在患有痴呆症的艾滋病患者中水平升高。这些实验是 旨在研究HIV-1在大脑中感染的机制。这个 星形胶质细胞在大脑中作为HIV-1储存库的作用是 采用体外感染模式进行调查。

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.