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 (2004). Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting cyclophilin A. Nucleic acids research, 32(12), pp. 3752-3759. Oxford University Press 10.1093/nar/gkh715

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Schümperli, Daniel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0305-1048

Publisher:

Oxford University Press

Language:

English

Submitter:

Daniel Schümperli

Date Deposited:

12 May 2015 08:07

Last Modified:

27 Apr 2018 09:02

Publisher DOI:

10.1093/nar/gkh715

PubMed ID:

15254276

BORIS DOI:

10.7892/boris.68848

URI:

https://boris.unibe.ch/id/eprint/68848

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