This article is part of the supplement: Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts
Poster presentation
Inhibition of HIV-1 expression and replication by SOFA-HDV ribozymes against Tat and Rev mRNA sequences
1 Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, McGill University, Montréal, Canada
2 Department of Microbiology and Immunology, McGill University, Montréal, Canada
3 Experimental Medicine, McGill University, Montréal, Canada
4 CNRS UMR 5236, Université de Bordeaux 2, Bordeaux, France
5 RNA Group/Groupe ARN, Département de Biochimie, Université de Sherbrooke, Sherbrooke, Québec, Canada
6 CNRS UMR 5236-UMI/UMII, CPBS - Equipe ''Assemblage et Réplication des Rétrovirus'', Montpellier, France
Retrovirology 2009, 6(Suppl 2):P47 doi:10.1186/1742-4690-6-S2-P47
The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/6/S2/P47
| Published: | 24 September 2009 |
© 2009 Lainé et al; licensee BioMed Central Ltd.
Background
RNA-based compounds are promising methods to inactivate viruses. New specific hepatitis delta virus (HDV)-derived ribozymes are natural molecules that can be engineered to specifically target a viral RNA. We have designed specific on-off adapted (SOFA) HDV-ribozymes targeting the regions of the HIV-1 RNA in the Tat and Rev sequences.
Results
We show that these SOFA-HDV ribozymes cleave their Tat RNA target in vitro. They inhibit the Tat-mediated transactivation of HIV-1 long terminal repeat by up to 62 and 86% in luciferase and beta-galactosidase assays, respectively. Inactivation of transfected HIV pNL4-3 molecular clone reached a fourfold inhibition by reverse transcriptase assay of the supernatant and an almost undetectable Gag protein synthesis. In vivo RNA cleavage reached 66 and 86% for two of the tested ribozymes showing that the decrease in HIV production is due to the direct decline in spliced and unspliced viral RNA. These SOFA-HDV-ribozymes were able to target four HIV-1 strains, showing an extended potential to act on multiple HIV variants. When transfected before HIV-1 infection, they prevented incoming virus to be expressed.
Conclusion
Our results show that SOFA-HDV-ribozymes show a great potential to target HIV and to be used as therapeutic agents in gene therapy.