HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF THE NERVOUS-SYSTEM - PATHOGENETIC MECHANISMS
HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF THE NERVOUS-SYSTEM - PATHOGENETIC MECHANISMS
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DOI：
10.1002/ana.410330502
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发表时间：
1993-05-01
影响因子：
11.2
通讯作者：
GENDELMAN, HE
中科院分区：
文献类型：
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作者：
EPSTEIN, LG;GENDELMAN, HE
人类免疫缺陷病毒1型（HIV-1）感染中枢神经系统与成人和儿童的特征性病毒学、临床和神经病理学表现相关。脑和脊髓的生产性感染发生在血源性巨噬细胞、常驻小胶质细胞和多核巨细胞中。先前的研究暗示了hiv -1基因产物或hiv -1感染巨噬细胞分泌的因子对神经毒性的间接机制。然而，这并不能解释少数感染细胞和广泛的组织病理之间的矛盾。根据我们实验室最近的研究，我们认为hiv -1感染的巨噬细胞可以启动神经毒性，然后通过与星形胶质细胞的细胞间相互作用放大。巨噬细胞-星形胶质细胞相互作用产生细胞因子肿瘤坏死因子- α和白细胞介素-1 β和花生四烯子代谢物，引起星形胶质细胞增殖和神经元损伤。不可避免地，星形胶质细胞增生放大了这些细胞过程，而脑感染在巨噬细胞和小胶质细胞中维持自身，也可能在星形胶质细胞中（通过限制性感染）。这些发现结合在一起，为在HIV-1疾病期间低数量的有效感染细胞如何引发进行性和毁灭性的神经损伤提供了新的见解，并提出了中断病理过程的治疗策略。
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with characteristic virological, clinical, and neuropathological findings in adults and children. Productive infection in the brain and spinal cord occurs in blood-derived macrophages, resident microglia, and multinucleated giant cells. Previous work implicated indirect mechanisms for neurotoxicity by HIV-I gene products or by factors secreted from HIV-1-infected macrophages. However, this cannot explain the paradox between the small numbers of infected cells and the widespread tissue pathology. Based on recent studies from our laboratories, we suggest that HIV-1-infected macrophages can initiate neurotoxicity, which is then amplified through cell-to-cell interactions with astrocytes. Macrophage-astrocyte interactions produce cytokines tumor necrosis factor-alpha and interleukin-1beta and arachidonic metabolites that cause astroglial proliferation and neuronal injury. Inevitably, the astrogliosis serves to amplify these cellular processes while brain infection maintains itself in macrophage and microglia and possibly in astrocytes (by restricted infection). These findings, taken together, provide fresh insights into how low numbers of productively infected cells could elicit progressive and devastating neurological impairment during HIV-1 disease, and suggest therapeutic strategies to interrupt the pathological process.