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Equipe de lInterferon 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-
Th1-type cytokines and of the ß-chemokines
macrophage-inflammatory protein-1
, 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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