Volume 6 Supplement 2

Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Open Access

Inhibition of HIV-1 expression and replication by SOFA-HDV ribozymes against Tat and Rev mRNA sequences

  • Sébastien Lainé1, 2, 4,
  • Robert J Scarborough1, 2,
  • Dominique Lévesque5,
  • Ludovic Didierlaurent6,
  • Kaitlin J Soye1, 2,
  • Marylène Mougel6,
  • Jean-Pierre Perreault5 and
  • Anne Gatignol1, 2, 3
Retrovirology20096(Suppl 2):P47


Published: 24 September 2009


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.


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.


Our results show that SOFA-HDV-ribozymes show a great potential to target HIV and to be used as therapeutic agents in gene therapy.

Authors’ Affiliations

Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, McGill University
Department of Microbiology and Immunology, McGill University
Experimental Medicine, McGill University
CNRS UMR 5236, Université de Bordeaux 2
RNA Group/Groupe ARN, Département de Biochimie, Université de Sherbrooke
CNRS UMR 5236-UMI/UMII, CPBS - Equipe ''Assemblage et Réplication des Rétrovirus''


© Lainé et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.