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首页> 外文期刊>Acta biomaterialia >An aptamer that binds efficiently to the hemagglutinins of highly pathogenic avian influenza viruses (H5N1 and H7N7) and inhibits hemagglutinin-glycan interactions
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An aptamer that binds efficiently to the hemagglutinins of highly pathogenic avian influenza viruses (H5N1 and H7N7) and inhibits hemagglutinin-glycan interactions

机译：高致病性禽流感病毒（H5N1和H7N7）有效地结合的适体，并抑制血凝素 - 甘油相互作用

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Highly pathogenic avian influenza (HPAI) H5 and H7 viruses have ravaged the poultry industry in numerous countries in Asia, Europe, Africa and the Middle East, and have resulted in the deaths of millions of birds. Although HPAI H5N1 viruses currently remain avian viruses, they are continuously evolving and have the potential to become pandemic-type viruses capable of human-human transmission. To develop specific reagents to allow better preparedness against this threat, we selected an aptamer (8-3) from a completely random RNA pool that binds with high affinity (～KD 170 pM) to the hemagglutinins (HAs) derived from HPAI H5N1 (A/H5N1/Vietnam/1194/2004 and A/H5N1/Indonesia/05/ 2005) and H7N7 (A/H7N7/Netherlands/219/2003) influenza A viruses. Aptamer 8-3 was able to efficiently distinguish HAs derived from subtypes of influenza A virus other than H5 and H7. Aptamer 8-3 was analyzed further to assess its ability to interfere with HA-glycan interactions using our previously established SPR-based competitive assay, and we found that aptamer 8-3 efficiently interferes with HA-glycan binding (EC50 ～ 25 nM). To derive shorter variants for other applications, aptamer 8-3 was shortened to a 44-mer by deletion analyses. The shortened aptamer, 8-3S, retains the full-length aptamer's affinity and specificity for its cognate Has, and also interferes with HA-glycan interactions. These studies suggest that aptamer 8-3S should be studied further to explore its potential applications not only in surveillance and diagnosis, but also in the development of H5N1- and H7N7-specific virucidal products that interfere with virus-host interactions to contain future H5N1 and H7N7 pandemics.
机译：高致病性禽流感（HPAI）H5和H7病毒在亚洲，欧洲，非洲和中东的众多国家遭受了蹂躏，并导致了数百万鸟类的死亡。虽然HPAI H5N1病毒目前仍然是禽类病毒，但它们是不断发展的，并且有可能成为能够进行人类传播的大流行型病毒。开发特定试剂以允许更好地对这种威胁进行准备，我们从完全随机的RNA池中选择一个适体（8-3），所述完全随机的RNA池与高亲和力（〜Kd 170 PM）结合到衍生自HPAI H5N1的血凝素（a）（a / H5N1 /越南/ 1194/2004和A / H5N1 / Indonesia / 05/05 / 05/2005）和H7N7（A / H7N7 / Netherlands / 219/219 / 2003）流感病毒。适体8-3能够有效地区分衍生自甲状腺素的亚型，除H5和H7以外的病毒。进一步分析适体8-3以评估使用我们先前建立的SPR基竞争性测定干扰Ha-Glycan相互作用的能力，并且我们发现适体8-3有效地干扰Ha-聚糖结合（EC50〜25nm）。为了获得其他应用的更短的变体，通过删除分析将Aptamer 8-3缩短为44-mer。缩短的适体，8-3s保留全长适体的亲和力，对其同源的亲和力和特异性具有，并且还干扰了Ha-聚糖的相互作用。这些研究表明，应进一步研究适体8-3S，不仅在监测和诊断中探讨其潜在应用，而且还在干扰病毒 - 宿主相互作用的H5N1和H7N7特异性毒性产品中，以遏制未来H5N1和H7N7 Pandemics。

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