Molecular mechanisms in the pathogenesis of AIDS encephalopathy.
While progress has been made in our knowledge of the natural history of HIV infections, an understanding of the molecular pathogenesis of AIDS encephalopathy remains to be determined. Previously we demonstrated that apoptosis and a deficiency of natural killer (NK) cell activity may play significant roles in the progression of HIV infections. We also reported that intracerebral co-injection of a recombinant HIV-1 fusion protein plus an excitatory amino acid agonist into neonatal rats synergistically produced brain pathology. Here we examine: 1) the effects of the HIV-1 envelope protein, gp-120, on neonatal rat astrocytes in vitro; 2) the spontaneous apoptosis of human neonatal and adult mononuclear leukocytes and, 3) the selective inhibition of NK activity cell from adult AIDS patients by the HIV-1 protein that caused brain pathology in neonatal rats. We demonstrate that gp-120 suppresses fas gene expression, a marker for apoptosis, by neonatal rat astrocytes. Neonatal human mononuclear leukocytes manifest spontaneous apoptosis as measured by DNA ladder formation while cells from adult donors do not. Direct addition of the HIV-1 protein to mononuclear cells in vitro selectively suppressed the NK cell activity from AIDS patients. These results support our premise that HIV-1 proteins are involved in the pathogenesis of AIDS encephalopathy.
Schwartz
S A
SA
Department of Medicine, State University of New York at Buffalo, Buffalo General Hospital 14203, USA.
Nair
M P
MP
D015526:AIDS Dementia Complex / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015686:Gene Products, env / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor / Q000235:genetics
D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019014:fas Receptor