Infection by HIV-1 is associated with a predominantly sensory axonal neuropathy. Pathological studies reveal infiltration by macrophages and microglial cells that harbor HIV-l, and there is no evidence for direct infection of neurons or Schwann cells. The neuropathy may be mediated by the interaction of HIV-l infected macrophages with neuronal cells. The gpl2O glycoprotein of HIV-l binds to the surface of sensory peripheral nerve neurons in the rat dorsal root ganglia and to human neuroblastoma cells. Preliminary studies suggest that the receptor is a glycoprotein. The gpl2o binding is eliminated by pretreating the cells with trypsin but not with chloroform-methanol, and the binding is blocked by a monoclonal antibody to galactocerebroside that cross reacts with neuronal glycoproteins.
The specific aims of the proposed project are as follows: 1) to identify and isolate the neuronal receptor by immunoprecipitation from the surface of radiolabeled neuronal cells and separation by Western blot, 2) to determine its primary structure by sequence analysis of its isolated cDNA clone, 3) to investigate its distribution in the nervous system, and 4) to determine if it could mediate the adhesion of gpl2O expressing monocytes to neurons which could injure the cells. This information could help elucidate the mechanism of neuropathy in HIV-l infection, and possibly lead to the development of specific and effective therapy.
| McAlarney, T; Ogino, M; Apostolski, S et al. (1995) Specificity and cross-reactivity of anti-galactocerebroside antibodies. Immunol Invest 24:595-606 |
