Interferon-gamma-activated monocytes impair infectivity of HIV particles by an oxygen metabolite-dependent reaction.
Mononuclear phagocytes generate microbicidal oxygen metabolites spontaneously and after phagocytic stimulation by a NADPH-dependent enzymatic reaction called the oxidative burst. The spontaneous release of reactive oxygen radicals and intermediates (ROI) increases five- to eightfold after treatment of monocytes with the lymphokine interferon-gamma (IFN-gamma). The effect of the IFN-gamma-activated release of ROI by human monocytes on the infectivity of free human immunodeficiency virus (HIV) in the supernatant was investigated with the following results. First, IFN-gamma-activated, but neither control monocytes nor lipopolysaccharide-stimulated monocytes effectively decreased the infectivity of cell-free HIV-1 in culture medium supernatant. Second, the mechanism of inactivation was dependent on the enhanced spontaneous release of ROI by IFN-gamma-activated mononuclear phagocytes, since either the enzyme catalase or the free radical scavenger butylated hydroxyanisole (BHA) could block this activity. Third, soluble and solid-phase HIV-1 outer envelope glycoprotein (gp120) failed to trigger the oxidative burst activity after specific gp120-monocytic CD4 receptor interaction. These results indicate an anti-viral effect of IFN-gamma-activated monocytes/macrophages on HIV-1 which may have important implications for our understanding of spread of the virus in the body and the development of full-blown AIDS after a long period of latency.
Ennen
J
J
Paul-Ehrlich Institute, Department of Biotechnology, Langen, Germany.
Kurth
R
R
D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins
D015699:HIV Envelope Protein gp120; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D002083:Butylated Hydroxyanisole; D007371:Interferon-gamma; D002374:Catalase; D010100:Oxygen