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

胎儿脑细胞培养物和儿科艾滋病脑组织中的 HIV-1 感染

• 批准号: 6163063
• 负责人: E O MAJOR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6163063
• 关键词: HIV infections; astrocytes; cell type; embryo /fetus tissue /cell culture; enzyme activity; enzyme inhibitors; gel mobility shift assay; gene expression; human fetus tissue; human immunodeficiency virus 1; human tissue; interleukin 1; latent virus infection; mixed tissue /cell culture; neurotrophic factors; pancreatic ribonuclease; pediatric AIDS; phorbols; protein kinase; transfection; tumor necrosis factor alpha; virus genetics; virus infection mechanism; virus protein; virus replication

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.

为了研究HIV-I分离株对神经系统的趋向性