Inhibition of HIV replication: A powerful antiviral strategy by IFN-β gene delivery in CD4+ cells

In this study, we demonstrated the efficiency and feasibility of a gene therapy protocol against HIV infection using the antiviral effects of IFN-β expression. Lentiviral vectors containing the human or the simian IFN-β sequences under the influence of the murine moderate H2-kb promoter were constructed. To examine the capacity of IFN-β to inhibit the replication of HIV in human CD4+ cells, a transduction protocol permitting to efficiently transduce CD4+ cells or PBMC (85 ± 12% of CD4+-transduced cells) with a moderate expression of IFN-β was developed. Results indicate that enforced expression of IFN-β has no negative effects in terms of apoptosis and proliferation. In human CD4+ cells, it drastically inhibits (up to 99.9%) replication after challenging with different strains of HIV-1. The expression of exogenous IFN-β leads to an amplification of the CD4+ cells (11-fold) and to a drastic decrease of the p24 protein. Micro-array analyses indicated that antiviral effect of IFN-β could be due to a major regulation of the inflammatory response. These results are encouraging for the development of a clinical study of gene therapy against AIDS using IFN-β.