Oligonucleotide-poly(L-lysine)-heparin complexes: potent sequence-specific inhibitors of HIV-1 infection.
Poly(L-lysine)-conjugated oligonucleotides complementary to the translation initiation region of the tat protein were tested for their capacity to inhibit HIV-1 replication in de novo infected cells. Sequence-specific antiviral effects were observed with these conjugates at 0.5 microM; their activity was transient, and the viral production was only delayed for a few days. Interestingly, their efficiency was significantly increased by the addition of heparin, a sulfated polyanion that also presents antiviral properties against HIV-1. A single addition, at the time of virus exposure, of the ternary complex formed between oligonucleotide-poly(L-lysine) (75 nM) and heparin (50 micrograms/mL) totally protects cells from HIV-1 infection. Primary interference with virus adsorption is essential for the strong antiviral effect. However, this protection remains strictly sequence specific as demonstrated in experiments performed with different HIV-1 isolates. As comparison, treatments that combine AZT and heparin at the same concentrations did not promote such a complete protection.
Degols
G
G
Institut de Génétique Moléculaire Montpellier, CNRS-Université de Montpellier, France.
Devaux
C
C
Lebleu
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000838:Anions; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D004279:DNA, Viral / Q000032:analysis; D004357:Drug Synergism; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D006493:Heparin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000627:therapeutic use*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000838:Anions; D000998:Antiviral Agents; D004279:DNA, Viral; D009841:Oligonucleotides; D013431:Sulfates; C042745:polylysine-heparin; D011107:Polylysine; D006493:Heparin