Didierlaurent, Ludovic

Gatignol, Anne

Lainé, Sébastien

Lévesque, Dominique

Mougel, Marylène

Perreault, Jean-Pierre

Scarborough, Robert J

Soye, Kaitlin J

Retrovirology

English

PubMed

Sébastien Lainé

Robert J Scarborough

Dominique Lévesque

Ludovic Didierlaurent

Kaitlin J Soye

Marylène Mougel

Jean-Pierre Perreault

Anne Gatignol

Crossref

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

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BioMed Central
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(page number not for citation purposes)
Retrovirology
Open AccessPoster presentation
Inhibition of HIV-1 expression and replication by SOFA-HDV 
ribozymes against Tat and Rev mRNA sequences
Sébastien Lainé*1,2,4, Robert J Scarborough1,2, Dominique Lévesque5, 
Ludovic Didierlaurent6, Kaitlin J Soye1,2, Marylène Mougel6, Jean-
Pierre Perreault5 and Anne Gatignol1,2,3
Address: 1Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, McGill University, Montréal, Canada, 2Department of 
Microbiology and Immunology, McGill University, Montréal, Canada, 3Experimental Medicine, McGill University, Montréal, Canada, 4CNRS 
UMR 5236, Université de Bordeaux 2, Bordeaux, France, 5RNA Group/Groupe ARN, Département de Biochimie, Université de Sherbrooke, 
Sherbrooke, Québec, Canada and 6CNRS UMR 5236-UMI/UMII, CPBS - Equipe ''Assemblage et Réplication des Rétrovirus'', Montpellier, France
* Corresponding author    
Background
RNA-based compounds are promising methods to inacti-
vate viruses. New specific hepatitis delta virus (HDV)-
derived ribozymes are natural molecules that can be engi-
neered 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 transac-
tivation of HIV-1 long terminal repeat by up to 62 and
86% in luciferase and beta-galactosidase assays, respec-
tively. Inactivation of transfected HIV pNL4-3 molecular
clone reached a fourfold inhibition by reverse tran-
scriptase assay of the supernatant and an almost undetec-
table 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.
from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts
Montpellier, France. 21-23 September 2009
Published: 24 September 2009
Retrovirology 2009, 6(Suppl 2):P47 doi:10.1186/1742-4690-6-S2-P47
<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S2/P47
© 2009 Lainé et al; licensee BioMed Central Ltd. 


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

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