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Original article

The guanine-quadruplex aptamer 93del inhibits HIV-1 replication ex vivo by interfering with viral entry, reverse transcription and integration

Aurélie Faure-Perraud, Mathieu Métifiot, Sandrine Reigadas, Patricia Recordon-Pinson, Vincent Parissi, Michel Ventura, Marie-Line Andréola

Corresponding author name: Marie-Line Andréola
Corresponding author e-mail: marie-line.andreola@reger.u-bordeaux2.fr

Citation: Antiviral Therapy 2011; 16:383-394
doi: 10.3851/IMP1756

Date accepted: 24 September 2010
Date published online: 16 March 2011

Abstract

Background: We have previously identified the guanine-rich oligonucleotide (ODN) 93del as a potent inhibitor in vitro of HIV-1 integrase. Moreover, low nanomolar concentrations of ODN 93del have been shown to inhibit HIV-1 replication in infected cells.

Methods: To investigate the ex vivo mechanism of ODN 93del inhibition, we analysed its antiviral effects on the early steps of HIV-1 replication such as viral entry, reverse transcription and integration using quantitative PCR.

Results: In addition to the effect on viral entry previously described for other guanine-quadruplex ODNs, transfection experiments showed that ODN 93del severely affects the proviral integration step independently of the effect on viral entry. Moreover, incubation of viral particles with ODN 93del revealed a potential microbicide activity of the aptamer.

Conclusions: Our data point to an original multimodal inhibition of HIV-1 replication by ODN 93del, strongly suggesting that targets of guanine-quartet-forming ODNs involve entry as well as other intracellular early steps of HIV-1 replication.

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