NEUROIMMUNOLOGY AND NEUROPATHOGENESIS OF HIV INFECTION

人类星形胶质细胞是在培养中培养出来的，并显示出能分泌 在慢性感染的前单核细胞克隆中刺激HIV-1的表达， U1.1.5。白介素6，在实验室中被其他人证明与之协同作用 肿瘤坏死因子-α在刺激U1.1.5细胞HIV-1表达中的作用细胞，被检测到 人和大鼠星形胶质细胞条件培养液。转化生长因子β (转化生长因子-β)在带状疱疹病毒感染的人脑中检测到 人和大鼠星形胶质细胞暴露于HIV-1的体外研究。发现白介素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。这种刺激是在转录后调控的 原代大鼠星形胶质细胞的时间和剂量依赖方式。这些细胞 在体外也被证明可以分泌和结合内皮素-3 a 血管收缩药。大鼠颗粒神经元暴露于HIV-1导致其 死亡。HIV-1脑部分离株BRVA是测试中最有效的分离株 神经元和神经突起的破坏。综合来看，这些结果 表明直接和间接机制都可能在 HIV-1感染的神经发病机制及其间接机制可能 涉及星形细胞因子。

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.