title: The guanine-quadruplex aptamer 93del inhibits HIV-1 replication ex vivo by interfering with viral entry, reverse transcription and integration.
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.
authors.affiliation: UMR, CNRS, Université Victor Segalen, Bordeaux, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Faure-Perraud
authors.forename: Mathieu
authors.initials: M
authors.lastname: Métifiot
authors.forename: Sandrine
authors.initials: S
authors.lastname: Reigadas
authors.forename: Patricia
authors.initials: P
authors.lastname: Recordon-Pinson
authors.forename: Vincent
authors.initials: V
authors.lastname: Parissi
authors.forename: Michel
authors.initials: M
authors.lastname: Ventura
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Andréola
mesh_terms: D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D004279:DNA, Viral / Q000032:analysis; D054856:G-Quadruplexes; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D016133:Polymerase Chain Reaction / Q000379:methods; D048348:Reverse Transcription / Q000187:drug effects; D016662:Virus Integration / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D052157:Aptamers, Nucleotide; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors