Protective Effect of Interferon-α Against Cell-Mediated Human Immunodeficiency Virus Transmission Resulting from Coculture of Infected Lymphocytes with Fetal Trophoblasts

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Abstract
The hypothesis that the low transmission rate of HIV in utero may be due, in part, to the protective effect of IFN-producing placental trophoblasts was explored in vitro. The model consisted of H9 lymphocytes, as surrogates of maternal HIV-infected T cells, incubated for 3 h with JEG-3 trophoblasts in the presence of 10-fold dilutions of leukocyte-derived IFN-α (from 1000 to 0.1 IU/ml). The dose effect was monitored either directly, by measuring the levels of proviral DNA by PCR after a single round of infection, or indirectly, by coculturing infected JEG-3 with cord blood-derived MT-4 lymphocytes and determining the levels of p24 production by ELISA. Both assays revealed a dose-dependent blocking effect of IFN-α on cell-mediated HIV transmission. The complete inhibition of HIV infection was observed in the presence of 100 IU IFN-α. The efficacy of such a low dose could not be attributed to insufficient viral load because up to 108 infectious particles could be transmitted during cell-cell contact. An adhesion assay ruled out the possibility that IFN-α acts through prevention of lymphocyte-trophoblast contact. The results suggest that physiologic levels of IFN-α, present in the placental environment, may contribute to the protection of the fetus against HIV infection.