Inhibition of HIV-1 multiplication by a modified U7 snRNA inducing Tat and Rev exon skipping

Asparuhova, Maria; Marti, Gabriela; Liu, Songkai; Serhan, Fatima; Trono, Didier; Schümperli, Daniel (2007). Inhibition of HIV-1 multiplication by a modified U7 snRNA inducing Tat and Rev exon skipping. Journal of gene medicine, 9(5), pp. 323-334. Chichester: Wiley 10.1002/jgm.1027

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The HIV-1 regulatory proteins Tat and Rev are encoded by multiply spliced mRNAs that differ by the use of alternative 3' splice sites at the beginning of the internal exon. If these internal exons are skipped, the expression of these genes, and hence HIV-1 multiplication, should be inhibited. We have previously developed a strategy, based on antisense derivatives of U7 small nuclear RNA, that allows us to induce the skipping of an internal exon in virtually any gene. Here, we have successfully applied this approach to induce a partial skipping of the Tat, Rev (and Nef) internal exons. Three functional U7 constructs were subcloned into a lentiviral vector. Two of them strongly reduced the efficiency of lentiviral particle production compared to vectors carrying either no U7 insert or unrelated U7 cassettes. This defect could be partly or fully compensated by coexpressing Rev from an unspliced mRNA in the producing cell line. Upon stable transduction into CEM-SS or CEM T-lymphocytes, the most efficient of these constructs inhibits HIV-1 multiplication. Although the inhibition is not complete, it is more efficient in combination with another mechanism inhibiting HIV multiplication. Therefore, this new approach targeting HIV-1 regulatory genes at the level of pre-mRNA splicing, in combination with other antiviral strategies, may be a useful new tool in the fight against HIV/AIDS. Copyright (c) 2007 John Wiley & Sons, Ltd

Item Type:

Journal Article (Original Article)

Division/Institute:

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

UniBE Contributor:

Schümperli, Daniel

ISSN:

1099-498X

Publisher:

Wiley

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:57

Last Modified:

06 Dec 2013 13:49

Publisher DOI:

10.1002/jgm.1027

PubMed ID:

323-334

Web of Science ID:

000247051100001

URI:

https://boris.unibe.ch/id/eprint/24690 (FactScience: 52827)

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