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The Journal of Immunology, 2000, 164: 1582-1587.
Copyright © 2000 by The American Association of Immunologists

Retrovirally Mediated IFN-ß Transduction of Macrophages Induces Resistance to HIV, Correlated with Up-Regulation of RANTES Production and Down-Regulation of C-C Chemokine Receptor-5 Expression1

Isabelle Cremer2, Vincent Vieillard3 and Edward De Maeyer

Equipe de l’Interferon et des Cytokines, Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique Institut Curie, Orsay, France

Constitutive expression of IFN-ß 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-ß 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-ß transduction totally blocked secretion of proinflammatory cytokines after HIV infection. The constitutive IFN-ß production also resulted in an increased production of IL-12 and IFN-{gamma} Th1-type cytokines and of the ß-chemokines macrophage-inflammatory protein-1{alpha}, macrophage-inflammatory protein-1ß, 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-ß-mediated gene therapy. In addition to inhibiting HIV replication, IFN-ß transduction could have beneficial immune effects in HIV-infected patients by favoring cellular immune responses.




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