Myeloperoxidase is virucidal to human immunodeficiency virus type 1 (HIV-1) in the persistently infected CEM human T-cell line or in acutely infected human peripheral blood mononuclear cells, as judged by viral infectivity and P24 radioimmunoassay. HIV-1 was specifically inactivated by low doses of the human myeloperoxidase (1.4 to 14.3 mU/ml) and the cells were spared. A higher enzyme concentration (143 mU/m) was cytotoxic, but uninfected CEM cells and normal lymphocytes were resistant to -143 mU of myeloperoxidase per ml. The enzyme was virucidal with the Cl -present in medium and did not require exogenous H202.Catalase, an antioxidant enzyme, partially inhibited the virucidal effect of myeloperoxidase. Hence, the H202 probably came from the HIV-infected cells themselves. These in vitro findings indicate that the myeloperoxidase system is capable of inactivating HWV-1 of infected cells.Neutrophils and monocytes of several mammalian species contain in their primary lysosomal granules the heme enzyme myeloperoxidase (MPO). This enzyme and other mammalian peroxidases, such as the lactoperoxidase (LPO) in milk and saliva and eosinophil peroxidase in eosinophils, form a powerful microbicidal system which is effective against a number of microorganisms, including viruses (5, 13,14). Stimulation of neutrophils results in a respiratory burst with the metabolic production of H202 (2). In its presence, MPO oxidizes Cl -to produce hypochlorous acid, which has strong oxidant properties (10, 15).Individuals infected with the human immunodeficiency virus (HIV) were recently reported to have depressed glutathione levels in the plasma and lungs (3). Since glutathione, the most abundant intracellular thiol, plays a key role as an antioxidant, oxidant stress may now be considered a factor in the pathogenesis of AIDS (9).We (25)
Human T-cell lines and normal lymphocytes persistently or acutely co-infected with the human immunodeficiency virus type 1 (HIV-1) and mycoplasmas were found to release hydrogen peroxide (H2O2), a likely cause of oxidative stress in these cells. The spectrofluorometric measurement of H2O2 release from these cells, using the scopoletin fluorescence quenching technique, gave values of 16-84 p moles/10(6) cells/min. In CEM cells, H2O2 was released only when acutely co-infected with HIV-1 and mycoplasmas, and not when infected with either organism alone. Anti-mycoplasmal antibiotics strongly reduced H2O2 release, and improved cell viability without blocking virus replication. These results suggest that the simultaneous infection by HIV-1 and mycoplasma leads to the release of H2O2, a toxic and potentially lethal metabolite, which in vivo may contribute to HIV-1 pathogenicity.
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