Interferon-β-induced human immunodeficiency virus resistance in CD34+ human hematopoietic progenitor cells:: Correlation with a down-regulation of CCR-5 expression

To explore the possibility of conferring a long-term resistance against human immunodeficiency Virus (HIV) by a low continuous production of interferon-beta (IFN-beta) in hematopoietic progenitor cells, we transduced the human CD34(+) TF-1 cells with a retroviral vector ensuring IFN-beta production. The IFN-beta-transduction of TF-1 cells resulted in resistance to infection with HIV-LAI, as shown by the selective survival of IFN-beta-transduced CD4(+) cells and the protection against HIV-induced apoptosis. A similar response against HIV-LAI infection was obtained after pretreatment with 100 U/ml of recombinant IFN-alpha 2b or IFN-beta. In contrast, after the addition or macrophage cell tropic (M cell-tropic) HIV strain, a treatment with exogenous IFN-alpha 2b resulted in a greater than or equal to 10-fold lower protection compared with exogenous IFN-beta or IFN-beta transduction. This specific effect of IFN-beta on M cell-tropic HIV strains was correlated with a down-regulation of the CCR-5 chemokine receptor expression, corresponding to a novel antiviral effect of IFN-beta. (C) 1999 Academic Press.