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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：与高致病性禽流感病毒（H5N1和H7N7）的血凝素有效结合并抑制血凝素-聚糖相互作用的适体

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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病毒席卷了亚洲，欧洲，非洲和中东许多国家的家禽业，并导致数百万只禽鸟死亡。尽管HPAI H5N1病毒目前仍是禽类病毒，但它们仍在不断发展，并有可能成为能够通过人与人传播的大流行型病毒。为了开发特异性试剂以更好地应对这种威胁，我们从完全随机的RNA库中选择了适体（8-3），该适体以高亲和力（〜KD 170 pM）与源自HPAI H5N1的血凝素（HA）结合/ H5N1 / Vietnam / 1194/2004和A / H5N1 / Indonesiasia / 05/2005）和H7N7（A / H7N7 / Netherlands / 219/2003）甲型流感病毒。适体8-3能够有效地区分源自除H5和H7以外的甲型流感病毒亚型的HA。使用我们先前建立的基于SPR的竞争测定法进一步分析了适体8-3，以评估其干扰HA-聚糖相互作用的能力，我们发现适体8-3有效地干扰了HA-聚糖的结合（EC50〜25 nM）。为了获得用于其他应用的较短变体，通过缺失分析将适体8-3缩短至44聚体。缩短的适体8-3S保留了全长适体对其同源Has的亲和力和特异性，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，以探索其在监视和诊断中的潜在应用，以及在H5N1和H7N7特异性杀病毒产品的开发中，这些产物会干扰病毒-宿主相互作用以包含未来的H5N1和H7N7大流行。

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