Retrovirology

, 6:P47 | Cite as

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

  • Sébastien Lainé
  • Robert J Scarborough
  • Dominique Lévesque
  • Ludovic Didierlaurent
  • Kaitlin J Soye
  • Marylène Mougel
  • Jean-Pierre Perreault
  • Anne Gatignol
Open Access
Poster presentation
  • 925 Downloads

Keywords

Hepatitis Delta Virus Reverse Transcriptase Assay Incoming Virus Specific Hepatitis Direct Decline 

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.

Copyright information

© Lainé et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • Sébastien Lainé
    • 1
    • 2
    • 4
  • Robert J Scarborough
    • 1
    • 2
  • Dominique Lévesque
    • 5
  • Ludovic Didierlaurent
    • 6
  • Kaitlin J Soye
    • 1
    • 2
  • Marylène Mougel
    • 6
  • Jean-Pierre Perreault
    • 5
  • Anne Gatignol
    • 1
    • 2
    • 3
  1. 1.Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical ResearchMcGill UniversityMontréalCanada
  2. 2.Department of Microbiology and ImmunologyMcGill UniversityMontréalCanada
  3. 3.Experimental MedicineMcGill UniversityMontréalCanada
  4. 4.CNRS UMR 5236Université de Bordeaux 2BordeauxFrance
  5. 5.RNA Group/Groupe ARN, Département de BiochimieUniversité de SherbrookeSherbrookeQuébecCanada
  6. 6.CNRS UMR 5236-UMI/UMIICPBS - Equipe ''Assemblage et Réplication des Rétrovirus''MontpellierFrance

Personalised recommendations