Retrovirally mediated IFN-beta transduction of macrophages induces resistance to HIV, correlated with up-regulation of RANTES production and down-regulation of C-C chemokine receptor-5 expression.
J Immunol
; 164(3): 1582-7, 2000 Feb 01.
Article
in En
| MEDLINE
| ID: mdl-10640778
ABSTRACT
Constitutive expression of IFN-beta 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-beta 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-beta transduction totally blocked secretion of proinflammatory cytokines after HIV infection. The constitutive IFN-beta production also resulted in an increased production of IL-12 and IFN-gamma Th1-type cytokines and of the beta-chemokines macrophage-inflammatory protein-1alpha, macrophage-inflammatory protein-1beta, 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-beta-mediated gene therapy. In addition to inhibiting HIV replication, IFN-beta transduction could have beneficial immune effects in HIV-infected patients by favoring cellular immune responses.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retroviridae
/
Down-Regulation
/
Up-Regulation
/
HIV-1
/
Interferon-beta
/
Chemokine CCL5
/
Receptors, CCR5
/
Macrophages
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunol
Year:
2000
Document type:
Article
Affiliation country:
France