Inhibition of HIV replication: a powerful antiviral strategy by IFN-beta 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-beta expression. Lentiviral vectors containing the human or the simian IFN-beta sequences under the influence of the murine moderate H2-kb promoter were constructed. To examine the capacity of IFN-beta 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-beta was developed. Results indicate that enforced expression of IFN-beta 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-beta 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-beta 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-beta.
Laboratory of Virology & Immunology, University of Liège, B-4000 Liège, Belgium.
Fabienne
F
Brule
Emmanuel
E
Khatissian
Alexandre
A
Benani
Audrey
A
Bodeux
Luc
L
Montagnier
Jacques
J
Piette
Evelyne
E
Lauret
Emmanuel
E
Ravet
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D049109:Cell Proliferation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000187:drug effects*; D000882:Haplorhini; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016899:Interferon-beta / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D014161:Transduction, Genetic; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D016899:Interferon-beta