title: DNA aptamers selected against the HIV-1 RNase H display in vitro antiviral activity.
abstract: The DNA polymerase of the human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a target widely used to inhibit HIV-1 replication. In contrast, very few inhibitors of the RNase H activity associated with RT have been described, despite the crucial role played by this activity in viral proliferation. DNA ligands with a high affinity for the RNase H domain of HIV-1 RT were isolated by systematic evolution of ligands by an exponential enrichment strategy (SELEX), using recombinant RTs with or without the RNase H domain. The selected oligonucleotides (ODNs) were able to inhibit in vitro the HIV-1 RNase H activity, while no effect was observed on cellular RNase H. We focused our interest on two G-rich inhibitory oligonucleotides. Model studies of the secondary structure of these ODNs strongly suggested that they were able to form G-quartets. In addition to the inhibition of HIV-1 RNase H observed in a cell free system, these ODNs were able to strongly diminish the infectivity of HIV-1 in human infected cells. Oligonucleotides described here may serve as leading compounds for the development of specific inhibitors of this key retroviral enzyme activity.
authors.affiliation: UMR 5097 CNRS-Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux Cedex, France. marie-line.andreola@reger.u-bordeaux2.fr
authors.forename: M L
authors.initials: ML
authors.lastname: Andreola
authors.forename: F
authors.initials: F
authors.lastname: Pileur
authors.forename: C
authors.initials: C
authors.lastname: Calmels
authors.forename: M
authors.initials: M
authors.lastname: Ventura
authors.forename: L
authors.initials: L
authors.lastname: Tarrago-Litvak
authors.forename: J J
authors.initials: JJ
authors.lastname: Toulmé
authors.forename: S
authors.initials: S
authors.lastname: Litvak
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000502:physiology; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry*; D015195:Drug Design; D015723:Gene Library; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D016914:Ribonuclease H / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D004279:DNA, Viral; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D054303:HIV Reverse Transcriptase; D016914:Ribonuclease H; D001616:beta-Galactosidase