Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons
Schwann cell chemokine receptors mediate HIV-1 gp120 toxicity to sensory neurons
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DOI：
10.1002/ana.10645
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发表时间：
2003-09-01
影响因子：
11.2
通讯作者：
Hoke, A
中科院分区：
文献类型：
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作者：
Keswani, SC;Polley, M;Hoke, A
人类免疫缺陷病毒（HIV）相关感觉神经病变（HIV- sn）是HIV感染最常见的神经系统并发症。目前，HYV-SN的发病机制尚不清楚。由于没有令人信服的神经元感染证据，HIV的神经毒性可能是由分泌的病毒蛋白（如包膜糖蛋白gp120）或被感染/活化的胶质细胞释放的神经毒性细胞因子影响的。我们描述了gp120对初级感觉神经元的毒性模型，其中gp120诱导神经变性和神经元凋亡。我们发现雪旺细胞，包裹周围神经轴突的细胞，传统上被认为具有被动的支持作用，介导了这种神经毒性。gp120将趋化因子受体CXCR4连接到雪旺细胞上，导致RANTES释放，诱导背根神经节神经元产生肿瘤坏死因子- α，随后以自分泌方式产生tnfr1介导的神经毒性。这种新描述的雪旺细胞-神经元相互作用可能不仅与HIV-SN有关，而且与其他周围神经病变有关。
Human immunodeficiency virus (HIV)-associated sensory neuropathy (HIV-SN) is the most common neurological complication of HIV infection. Currently, the pathogenesis of HYV-SN is unknown. Because there is no convincing evidence of neuronal infection, HIV neurotoxicity is likely to be effected either by secreted viral proteins such as the envelope glycoprotein gp120 or by neurotoxic cytokines released from infected/activated glial cells. We describe a model of gp120 toxicity to primary sensory neurons, in which gp120 induces neuritic degeneration and neuronal apoptosis. We show that Schwann cells, the cells that ensheath peripheral nerve axons, and which traditionally have been viewed as having a passive, supporting role, mediate this neurotoxicity. Ligation of the chemokine receptor CXCR4 on Schwann cells by gp120 resulted in the release of RANTES, which induced dorsal root ganglion neurons to produce tumor necrosis factor-alpha and subsequent TNFR1-mediated neurotoxicity in an autocrine fashion. This newly described Schwann cell-neuron interaction may be pathogenically relevant not only in HIV-SN but also in other peripheral neuropathies.