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Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting cyclophilin A

Liu, Songkai ; Asparuhova, Maria ; Brondani, Vincent ; Ziekau, Ingrid ; Klimkait, Thomas ; Schümperli, Daniel

In: Nucleic Acids Research, 2004, vol. 32, no. 12, p. 3752-3759

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    Titre
    • Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting cyclophilin A
    Auteur
    • Liu, Songkai. Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland and
    • Asparuhova, Maria. Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland and
    • Brondani, Vincent. Institute of Medical Microbiology, University of Basel, Petersplatz 10, 4003 Basel, Switzerland
    • Ziekau, Ingrid. Institute of Medical Microbiology, University of Basel, Petersplatz 10, 4003 Basel, Switzerland
    • Klimkait, Thomas. Institute of Medical Microbiology, University of Basel, Petersplatz 10, 4003 Basel, Switzerland
    • Schümperli, Daniel. Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland and
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Nucleic Acids Research, 2004, vol. 32, no. 12, p. 3752-3759. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:301119
    Summary
    Human immunodeficiency virus 1 (HIV-1) multiplication depends on a cellular protein, cyclophilin A (CyPA), that gets integrated into viral particles. Because CyPA is not required for cell viability, we attempted to block its synthesis in order to inhibit HIV-1 replication. For this purpose, we used antisense U7 small nuclear RNAs (snRNAs) that disturb CyPA pre-mRNA splicing and short interfering RNAs (siRNAs) that target CyPA mRNA for degradation. With dual-specificity U7 snRNAs targeting the 3′ and 5′ splice sites of CyPA exons 3 or 4, we obtained an efficient skipping of these exons and a strong reduction of CyPA protein. Furthermore, short interfering RNAs targeting two segments of the CyPA coding region strongly reduced CyPA mRNA and protein levels. Upon lentiviral vector-mediated transduction, prolonged antisense effects were obtained for both types of antisense RNAs in the human T-cell line CEM-SS. These transduced CEM-SS cells showed a delayed, and for the siRNAs also reduced, HIV-1 multiplication. Since the two types of antisense RNAs function by different mechanisms, combining the two approaches may result in a synergistic effect