Retrovirally Mediated IFN-β Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression

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Abstract
Constitutive expression of IFN-β by HIV target cells may be an alternative or complementary therapeutic approach for the treatment of AIDS. We show that macrophages derived from CD34+ cells from umbilical cord blood can be efficiently transduced by a retroviral vector carrying the IFN-β coding sequence. This results in resistance to infection by a macrophage-tropic HIV type 1, as shown by the drastic reduction in the HIV DNA copy number per cell and in p24 release. Moreover, IFN-β transduction totally blocked secretion of proinflammatory cytokines after HIV infection. The constitutive IFN-β production also resulted in an increased production of IL-12 and IFN-γ Th1-type cytokines and of the β-chemokines macrophage-inflammatory protein-1α, macrophage-inflammatory protein-1β, and RANTES. RANTES was found to be involved in the HIV resistance observed, and this was correlated with a down-regulation of the CCR-5 HIV entry coreceptor. These results demonstrate the feasibility and the efficacy of such IFN-β-mediated gene therapy. In addition to inhibiting HIV replication, IFN-β transduction could have beneficial immune effects in HIV-infected patients by favoring cellular immune responses.