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 concentration and motor functions. This neuronal injury, although related to the human immunodeficiency virus (HIV), occurs even though the neurons themselves are not infected by the virus. A complex web of interactions 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 human small intestine as a candidate for these noxious substances. This peptide is neither cell nor tumor specific and mediates cytolysis by membrane permeabilization based on membrane potential. The identified peptide is, however, type specific against viruses, only attacking enveloped viruses. This study hypothesizes that the peptide is sequestered in the HIV viral envelope and is released in very toxic concentrations when localized membrane potential is high. The peptide is localized in the Paneth cells of the human small intestine, and a transmission pathway is identified through the abrogation of intestinal tissue occurring during receptive anal intercourse. A study of amino acid sequences between this peptide and three variants of HIV confirmed homologies. The identification of this peptide as a possible mechanism could substantially alter AIDS treatment protocols.
Sangster
B
B
LaMond Institute, Huntington Beach, CA 92646, USA.
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission; D000595:Amino Acid Sequence; D015551:Autoimmunity; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology; D003603:Cytotoxins / Q000235:genetics / Q000276:immunology / Q000633:toxicity*; D023082:Defensins; D005260:Female; D006678:HIV / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000633:toxicity*
D001798:Blood Proteins; D003603:Cytotoxins; D023082:Defensins; D010455:Peptides; D014759:Viral Envelope Proteins