Jeon Sung Ho, Kayhan Basak, Ben-Yedidia Tamar, Arnon Ruth
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
J Biol Chem. 2004 Nov 12;279(46):48410-9. doi: 10.1074/jbc.M409059200. Epub 2004 Sep 8.
Influenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors. We describe a novel oligonucleotide, known also as an aptamer, which has been designed to complement the receptor-binding region of the influenza hemagglutinin molecule. It was constructed by screening a DNA library and processing by the selective evolution of ligands by exponential enrichment (SELEX) procedure. We show that this DNA aptamer is indeed capable of inhibiting the hemagglutinin capacity of the virus, as well as in the prevention of viral infectivity in vitro, in tissue culture. Furthermore, it inhibits viral infection by different influenza strains in an animal model, as manifested by 90-99% reduction of virus burden in the lungs of treated mice. The mode of action of this aptamer is by blocking the binding of influenza virus to target cell receptors and consequently prevention of the virus invasion into the host cells.
甲型流感病毒感染是全球发病和死亡的主要原因。目前控制流感的方法基于疫苗预防和现有的特异性流感神经氨酸酶抑制剂药物治疗。本研究采用的方法是通过特异性阻断病毒与宿主细胞受体的结合来预防和/或改善流感感染。我们描述了一种新型寡核苷酸,也称为适配体,它被设计用于与流感血凝素分子的受体结合区域互补。它是通过筛选DNA文库并通过指数富集配体的系统进化(SELEX)程序进行处理而构建的。我们表明,这种DNA适配体确实能够抑制病毒的血凝素能力,以及在体外组织培养中预防病毒感染性。此外,在动物模型中,它能抑制不同流感毒株的感染,表现为治疗小鼠肺部病毒载量降低90%-99%。这种适配体的作用方式是通过阻断流感病毒与靶细胞受体的结合,从而防止病毒侵入宿主细胞。