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

• Published in: Antiviral therapy Vol. 16; no. 3; pp. 383 - 394
• Main Authors: FAURE-PERRAUD, Aurélie, METIFIOT, Mathieu, REIGADAS, Sandrine, RECORDON-PINSON, Patricia, PARISSI, Vincent, VENTURA, Michel, ANDREOLA, Marie-Line
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.01.2011
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Aptamers, Nucleotide - pharmacology; Biological and medical sciences; DNA, Viral - analysis; G-Quadruplexes; HeLa Cells; HIV Integrase Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - pathogenicity; HIV-1 - physiology; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Life Sciences; Medical sciences; Microbiology and Parasitology; Pharmacology. Drug treatments; Polymerase Chain Reaction - methods; Reverse Transcription - drug effects; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virus Integration - drug effects; Virus Internalization - drug effects; Virus Replication - drug effects; Immunopathology; HIV-1 virus; Retroviridae; Reverse transcription; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Ex vivo; Viral disease; Replication; Aptamer; Human immunodeficiency virus
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP1756

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. 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. 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. 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.