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 在来自以下来源的培养物中引发各种 HIV-1 毒株的感染 人类胎儿的大脑。病毒吸附几天后 星形胶质细胞培养物，测量病毒抗原。 25 株中的 7 株分离出 经测试，来自脑脊液或血液，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 和确定的核苷酸序列。没有证据表明独特 该结合区的序列与感染的分离株相比 星形胶质细胞。然而，大多数传染性分离株 合胞体诱导表型，嗜淋巴细胞的特征 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 tat 能够 增加两种细胞蛋白质的活性。两者的转录 因子 NF-kB 和细胞蛋白激酶 PKC 表现出更高的 当星形胶质细胞用可溶性tat处理时的活性。的能力 HIV-1 调节细胞功能的因子可能有助于解释 几乎没有证据表明脑组织中的神经系统功能障碍 病毒的活跃繁殖。我们还发现 HIV-1 上调 β-趋化因子 MCP-1 的合成和释放也被发现 艾滋病患者痴呆症水平升高。这些实验是 旨在研究大脑中HIV-1感染的机制。的 星形胶质细胞作为大脑中 HIV-1 储存库的作用正在被研究 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.