IDENTIFICATION OF CYTOTOXIC PEPTIDE AS POSSIBLE MECHANISM FOR NEUROTOXICITY OF HIV VIRAL ENVELOPE AND AIDS PATHOGENESIS

A major segment of acquired immunodeficiency syndrome (AIDS) patients suffer from neurological complications, including impairments in conce ntration and motor functions. This neuronal injury, although related t o the human immunodeficiency virus (HIV), occurs even though the neuro ns themselves are not infected by the virus. A complex web of interact ions of the immune system with noxious substances released from gp120- stimulated macrophages is hypothesized as the mechanism of the injury. This study has identified an antimicrobial peptide resident in the hu man small intestine as a candidate for these noxious substances. This peptide is neither cell nor tumor specific and mediates cytolysis by m embrane permeabilization based on membrane potential. The identified p eptide is, however, type specific against viruses, only attacking enve loped viruses. This study hypothesizes that the peptide is sequestered in the HIV viral envelope and is released in very toxic concentration s when localized membrane potential is high. The peptide is localized in the Paneth cells of the human small intestine, and a transmission p athway is identified through the abrogation of intestinal tissue occur ring during receptive anal intercourse. A study of amino acid sequence s between this peptide and three variants of HIV confirmed homologies. The identification of this peptide as a possible mechanism could subs tantially alter AIDS treatment protocols.