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Antivir Ther. 2011;16(3):383-94. doi: 10.3851/IMP1756.

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

Author information

1
UMR, CNRS, Université Victor Segalen, Bordeaux, France.

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.

PMID:
21555821
DOI:
10.3851/IMP1756
[Indexed for MEDLINE]

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