title: Protective effect of interferon-alpha against cell-mediated human immunodeficiency virus transmission resulting from coculture of infected lymphocytes with fetal trophoblasts.
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-alpha (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-alpha on cell-mediated HIV transmission. The complete inhibition of HIV infection was observed in the presence of 100 IU IFN-alpha. The efficacy of such a low dose could not be attributed to insufficient viral load because up to 10(8) infectious particles could be transmitted during cell-cell contact. An adhesion assay ruled out the possibility that IFN-alpha acts through prevention of lymphocyte-trophoblast contact. The results suggest that physiologic levels of IFN-alpha, present in the placental environment, may contribute to the protection of the fetus against HIV infection.
authors.affiliation: Department of Biochemistry, New York University Medical Center, NY 10016, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Bourinbaiar
authors.forename: K
authors.initials: K
authors.lastname: Krasinski
authors.forename: W
authors.initials: W
authors.lastname: Borkowsky
authors.forename: S
authors.initials: S
authors.lastname: Lee-Huang
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000821:virology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011533:Proviruses / Q000235:genetics; D014327:Trophoblasts / Q000187:drug effects* / Q000821:virology
chemical_list: D004279:DNA, Viral; D016898:Interferon-alpha