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Inhibition of HIV-1 expression and replication by SOFA-HDV ribozymes against Tat and Rev mRNA sequences
Retrovirology volume 6, Article number: P47 (2009)
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.
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Correspondence to Sébastien Lainé.
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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Lainé, S., Scarborough, R.J., Lévesque, D. et al. Inhibition of HIV-1 expression and replication by SOFA-HDV ribozymes against Tat and Rev mRNA sequences. Retrovirology 6, P47 (2009). https://doi.org/10.1186/1742-4690-6-S2-P47
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Keywords
- Hepatitis Delta Virus
- Reverse Transcriptase Assay
- Incoming Virus
- Specific Hepatitis
- Direct Decline
