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)

Glucose oxidase and peroxidase (lactoperoxidase or myeloperoxidase) are virucidal to human immunodeficiency virus type 1 (HIV-1) in the presence of sodium iodide, as assessed by the loss of viral replication in a syncytium-forming assay or by the inhibition of cytopathic effects on infected cells. In the presence of low concentrations of sodium iodide, five HlV-1 isolates were equally susceptible to this virucidal system at enzyme concentrations of a few milliunits. The loss ofviral replication was linearly related to the time of incubation in the enzyme solutions, with an inactivation rate of 1 log unit every 30 min. These enzymes and this halide were also cytotoxic to chronically infected, but not to uninfected, cultured CEM cells. Protein conijugates were prepared by using the enzymes and murine antibody 105.34, which recognized the V3 loop of H1V-i LAT isolate surface glycoprotein, or recombinant human CD4. The protein conjugates inactivated free virus at rates similar to those of the free enzymes and were more effective than antibody or recombinant CD4 alone. These in vitro findings demonstrate that the peroxidase-H202-halide system provides potent virucidal activity against HIV-1.

It was previously reported that polystyrene substituted with the sulfonate group, PSSO3, which has anticoagulant heparin-like properties, and then coated with fibronectin supports the growth of human umbilical vein endothelial cells. On the other hand, polystyrene substituted with the amino acid sulfamide group, PSSO2-Asp, which has a higher anticoagulant activity, and then coated with fibronectin no longer supported the growth of endothelial cells. We report here that, while the affinity of fibronectin to either polymer is of the same order of magnitude, fibronectin is adsorbed onto the PSSO2-Asp polymer in a different conformation compared to the PSSO3 polymer. This was shown by a higher binding of polyclonal antifibronectin antibodies to fibronectin-coated PSSO2-Asp polymer, and by a decreased susceptibility of the coated fibronectin to proteolysis by thermolysin. This study provides evidence that a solid phase substrate with a strong heparin-like function may influence the conformation and biological properties of fibronectin.

Three levels of variation are described in the response to sheep red blood cells (SRBC). Inbred strains of mice are distinguishable in terms of early or late kinetics of IgM response, high or low overall IgG response, and the relative expression of IgG1, IgG2a and IgG2b antibody in their response to SRBC. Results using C57BL/10 hybrid progeny strongly suggest a genetic control of these different aspects of the anti-SRBC response. The IgM kinetic pattern and the quantitative IgG response are regulated by two independent multigenic systems. Evidence is also presented for a distinction between the genes controlling the quantitative IgG response and those which control the 7 S isotypic pattern. IgG2a antibody expression seems regulated by a single gene. Neither group of genes involved in these various types of regulation seems directly linked to the H-2 complex or to the CH allotype. The hypothesis that 4 different sets of genes might control IgM, IgG1, IgG2a and IgG2b expression is discussed.

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.