HIV-1 viral protein R causes peripheral nervous system injury associated with in vivo neuropathic pain

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Shaona AcharjeeC Power

Abstract

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 ([Ca(2+)]) 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 [Ca(2+)] and action potential frequency while increasing input resistance. HIV infection of human DRG cultures caused neurite retraction (P<0.05), accompanied by induction of interferon-α (IFN-α) transcripts (P<0.05). vpr/RAG1(-/-) mice expressed Vpr together with increased IFN-α (P<0.05) in the PNS and also exhibited mechanical allodynia, unlike their vpr/RAG...Continue Reading

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Citations

Sep 16, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Christopher PowerMaria Polyak
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Oct 12, 2016·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Manmeet K MamikChristopher Power
Feb 15, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Richard Y ZhaoMichael I Bukrinsky
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