Degols G, Devaux C, Lebleu B
Institut de Génétique Moléculaire Montpellier, CNRS-Université de Montpellier, France.
Bioconjug Chem. 1994 Jan-Feb;5(1):8-13. doi: 10.1021/bc00025a002.
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.
测试了与tat蛋白翻译起始区互补的聚（L-赖氨酸）缀合寡核苷酸在初感染细胞中抑制HIV-1复制的能力。在0.5微摩尔浓度下观察到这些缀合物具有序列特异性抗病毒作用；它们的活性是短暂的，病毒产生仅延迟几天。有趣的是，添加肝素（一种也具有抗HIV-1抗病毒特性的硫酸化聚阴离子）可显著提高其效率。在病毒暴露时单次添加由寡核苷酸-聚（L-赖氨酸）（75纳摩尔）和肝素（50微克/毫升）形成的三元复合物可完全保护细胞免受HIV-1感染。对病毒吸附的初级干扰对于强大的抗病毒作用至关重要。然而，如用不同HIV-1分离株进行的实验所示，这种保护仍严格具有序列特异性。作为比较，以相同浓度联合使用齐多夫定和肝素的处理并未促进如此完全的保护。
