Nerve Growth Factor Signaling Pathways Modulate HIV Vpr'sactions on Sensory Neurons: A Potential Target for Treatment of Distal Sensory Polyneuropathy in HIV/AIDS
- *Corresponding Author:
- Christine A. Webber
Division of Anatomy
Department of Surgery, University of Alberta
Edmonton, Alberta, Room 501
Medical Sciences Building, T6G 2H7, Canada
E-mail: [email protected]
Received date: May 19, 2014; Accepted date: July 28, 2014; Published date: August 10, 2014
Citation: Ballanyi K, Power C, Acharjee S, Webber CA (2014) Nerve Growth Factor Signaling Pathways Modulate HIV Vpr’sactions on Sensory Neurons: A Potential Target for Treatment of Distal Sensory Polyneuropathy in HIV/AIDS. J AIDS Clin Res 5:334. doi:10.4172/2155-6113.1000334
Copyright: © 2014 Ballanyi K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Over 35 million people are infected currently with the Human Immunodeficiency Virus (HIV), of whom 30-50% will experience Distal Sensory Polyneuropathy (DSP), usually causing paresthesiae and neuropathic pain, particularly in the feet. This presentation is identical to patients with Diabetic DSP. Current regimens for treating neuropathic pain have limited benefits. Thus, a deeper understanding of the mechanisms of HIV-DSP is imperative to permit the rational development of new therapies. Transgenic mice expressing the HIV-1 viral protein R (Vpr) show footpad epidermal denervation and allodynia as observed in HIV-infected patients. We found that exogenous Vpr inhibits axon outgrowth, causes hyperexcitability and increases cytosolic calcium in cultured dorsal root ganglion neurons (DRGN). Exposure of DRGN to nerve growth factor (NGF) or modulating NGF signaling pathways before Vpr treatment can block its effects. These findings will be extended to in vivo models to determine if altering the NGF signaling pathway can prevent Vprinduced denervation and allodynia.