HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain
HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain
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DOI：
10.1096/fj.10-162313
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发表时间：
2010-11-01
期刊：
影响因子：
4.8
通讯作者：
Power, Christopher
中科院分区：
文献类型：
--
作者：
Acharjee, Shaona;Noorbakhsh, Farshid;Power, Christopher
疼痛性周围神经病变已成为HIV/AIDS患者的主要神经系统疾病。在此，我们研究了细胞毒性HIV-1辅助蛋白，病毒蛋白R（Vpr），对周围神经系统（PNS）的影响。通过RT-PCR和免疫细胞化学研究了HIV感染者外周神经和HIV感染的人背根神经节（DRG）培养物中宿主和病毒基因的表达。在培养的DRG中分析胞浆钙（[Ca 2 +]）通量和神经元膜反应。在转基因小鼠模型中评估了神经行为反应和细胞因子水平，其中vpr转基因在免疫缺陷背景下表达（vpr/RAG 1（-/-））。在HIV感染者的外周神经和背根节中检测到Vpr转录本和蛋白。暴露于Vpr的大鼠或人培养的DRG神经元迅速增加[Ca 2 +]和动作电位频率，同时增加输入电阻。HIV感染的人背根神经节培养物引起神经突起回缩（P
Painful peripheral neuropathy has become the principal neurological disorder in HIV/AIDS patients. Herein, we investigated the effects of a cytotoxic HIV-1 accessory protein, viral protein R (Vpr), on the peripheral nervous system (PNS). Host and viral gene expression was investigated in peripheral nerves from HIV-infected individuals and in HIV-infected human dorsal root ganglion (DRG) cultures by RT-PCR and immunocytochemistry. Cytosolic calcium ([Ca2+]) fluxes and neuronal membrane responses were analyzed in cultured DRGs. Neurobehavioral responses and cytokine levels were assessed in a transgenic mouse model in which the vpr transgene was expressed in an immunodeficient background (vpr/RAG1(-/-)). Vpr transcripts and proteins were detected in peripheral nerves and DRGs from HIV-infected patients. Exposure of rat or human cultured DRG neurons to Vpr rapidly increased [Ca2+] and action potential frequency while increasing input resistance. HIV infection of human DRG cultures caused neurite retraction (P