Journal sur le SIDA et la recherche clinique

Nerve Growth Factor Signaling Pathways Modulate HIV Vpr'sactions on Sensory Neurons: A Potential Target for Treatment of Distal Sensory Polyneuropathy in HIV/AIDS

Abstract

Klaus Ballanyi, Christopher Power, Shaona Acharjee and Christine A Webber

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.