NEUROIMMUNOLOGY AND NEUROPATHOGENESIS OF HIV INFECTION

HIV 感染的神经免疫学和神经发病机制

• 批准号: 3809726
• 负责人: L VITKOVIC
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/3809726
• 关键词: HIV infections; astrocytes; gene expression; human immunodeficiency virus 1; interleukin 6; nervous system disorder; psychoneuroimmunology; transforming growth factors; vasoconstrictors; virus infection mechanism

Human astrocytes were grown in culture and shown to secrete molecules which stimulated HIV-1 expression in a chronically infected promonocytic clone, U1.1.5. Interleukin-6, shown by others in the laboratory to synergize with TNF-alpha in stimulating HIV-1 expression in U1.1.5. cells, was detected in human and rat astrocyte-conditioned media. Transforming growth factor beta (TGF-beta) was detected in herpes zoster virus-infected human brain and in human and rat astrocytes exposed to HIV-1 in vitro. Interleukin-1 was found to stimulate TGF-beta expression in cultured rat astrocytes, microglia and oligodendrocytes. This stimulation was regulated post-transcriptionally in a time- and dose-dependent manner in primary rat astrocytes. These cells were also shown in vitro to secrete and bind endothelin-3 a potent vasoconstrictor. Exposure of rat granule neurons to HIV-1 resulted in their death. Brain isolate of HIV-1 BRVA was the most potent isolate tested in the destruction of neurons and neurites. Taken together, these results suggest that both direct and indirect mechanisms may operate in the neuropathogenesis of HIV-1 infection and that the indirect mechanism may involve astrocytic cytokines.

人类星形胶质细胞在培养物中生长，并显示出分泌分子， 在慢性感染的前单核细胞克隆中刺激HIV-1表达， U1.1.5.白细胞介素-6，在实验室中被其他人证明与 TNF-α刺激U1.1.5中HIV-1的表达。细胞，检测到在 人和大鼠星形胶质细胞条件培养基。转化生长因子β 在带状疱疹病毒感染的人脑中检测到TGF-β， 体外暴露于HIV-1的人和大鼠星形胶质细胞。白细胞介素-1 刺激培养的大鼠星形胶质细胞、小胶质细胞和 少突胶质细胞这种刺激在转录后受到调节， 在原代大鼠星形胶质细胞中呈时间和剂量依赖性。这些细胞 在体外也显示出分泌和结合内皮素-3a， 血管收缩剂将大鼠颗粒神经元暴露于HIV-1导致其 死亡HIV-1 BRVA的脑分离株是受试的最有效分离株， 神经元和神经突的破坏。综合来看，这些结果 这表明，直接和间接的机制都可能在 HIV-1感染的神经发病机制，间接机制可能 包括星形胶质细胞细胞因子。