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首页> 外文期刊>Molecules >Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus
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Molecular Characterisation of the Haemagglutinin Glycan-Binding Specificity of Egg-Adapted Vaccine Strains of the Pandemic 2009 H1N1 Swine Influenza A Virus

机译：大流行2009 H1N1甲型流感病毒的蛋适应疫苗株血凝素聚糖结合特异性的分子表征。

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The haemagglutinin (HA) glycan binding selectivity of H1N1 influenza viruses is an important determinant for the host range of the virus and egg-adaption during vaccine production. This study integrates glycan binding data with structure-recognition models to examine the impact of the K123N, D225G and Q226R mutations (as seen in the HA of vaccine strains of the pandemic 2009 H1N1 swine influenza A virus). The glycan-binding selectivity of three A/California/07/09 vaccine production strains, and purified recombinant A/California/07/09 HAs harboring these mutations was examined via a solid-phase ELISA assay. Wild-type A/California/07/09 recombinant HA bound specifically to 2,6-linked sialyl-glycans, with no affinity for the 2,3-linked sialyl-glycans in the array. In contrast, the vaccine virus strains and recombinant HA harboring the Q226R HA mutation displayed a comparable pattern of highly specific binding to 2,3-linked sialyl-glycans, with a negligible affinity for 2,6-linked sialyl-glycans. The D225G A/California/07/09 recombinant HA displayed an enhanced binding affinity for both 2,6- and 2,3-linked sialyl-glycans in the array. Notably its 2,6-glycan affinity was generally higher compared to its 2,3-glycan affinity, which may explain why the double mutant was not naturally selected during egg-adaption of the virus. The K123N mutation which introduces a glycosylation site proximal to the receptor binding site, did not impact the 2,3/2,6 glycan selectivity, however, it lowered the overall glycan binding affinity of the HA; suggesting glycosylation may interfere with receptor binding. Docking models and per residues' scoring were employed to provide a structure-recognition rational for the experimental glycan binding data. Collectively, the glycan binding data inform future vaccine design strategies to introduce the D225G or Q226R amino acid substitutions into recombinant H1N1 viruses.
机译：H1N1流感病毒的血凝素（HA）聚糖结合选择性是疫苗生产过程中病毒宿主范围和卵适应性的重要决定因素。这项研究将聚糖结合数据与结构识别模型整合在一起，以检查K123N，D225G和Q226R突变的影响（如在2009年H1N1大流行性甲型流感病毒大流行疫苗株的HA中所见）。通过固相ELISA测定法检查了三种A / California / 07/09疫苗生产菌株和具有这些突变的纯化的重组A / California / 07/09 HAs的聚糖结合选择性。野生型A / California / 07/09重组HA与2,6-连接的唾液酸聚糖特异性结合，对阵列中2,3-连接的唾液酸聚糖没有亲和力。相反，具有Q226R HA突变的疫苗病毒株和重组HA表现出与2，3-连接的唾液酸聚糖高度特异性结合的可比模式，对2，6-连接的唾液酸聚糖的亲和力可忽略不计。 D225G A / California / 07/09重组HA对阵列中的2,6-和2,3-连接的唾液酸聚糖均显示出增强的结合亲和力。值得注意的是，其2，6-聚糖亲和力通常高于其2，3-聚糖亲和力，这可以解释为什么在病毒的卵适应过程中不能自然选择双重突变体。 K123N突变会在受体结合位点附近引入糖基化位点，但不会影响2,3 / 2,6聚糖的选择性，但是会降低HA的整体聚糖结合亲和力。提示糖基化可能会干扰受体结合。使用对接模型和每个残基的评分为实验聚糖结合数据提供结构识别的合理性。总的来说，聚糖结合数据为将来的疫苗设计策略提供了指导，将D225G或Q226R氨基酸取代引入重组H1N1病毒中。

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