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.
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 ODN93del have been shown to inhibit HIV-1 replication in infected cells. METHODS: To investigate the ex vivo mechanism of ODN93del 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 ODN93del severely affects the proviral integration step independently of the effect on viral entry. Moreover, incubation of viral particles with ODN93del revealed a potential microbicide activity of the aptamer. CONCLUSIONS: Our data point to an original multimodal inhibition of HIV-1 replication by ODN93del, strongly suggesting that targets of guanine-quartet-forming ODNs involve entry as well as other intracellular early steps of HIV-1 replication.
Authors: Rosalba Perrone; Elena Butovskaya; Sara Lago; Alfredo Garzino-Demo; Christophe Pannecouque; Giorgio Palù; Sara N Richter Journal: Int J Antimicrob Agents Date: 2016-03-11 Impact factor: 5.283