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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses
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Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses

机译：1918年大流行性甲型流感病毒传播能力差异的定量生化原理

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摘要

The human adaptation of influenza A viruses is critically governed by the binding specificity of the viral surface hemagglutinin (HA) to long (chain length) α2-6 sialylated glycan (α2-6) receptors on the human upper respiratory tissues. A recent study demonstrated that whereas the 1918 H1N1 pandemic virus, A/South Carolina/1/1918 (SC18), with α2-6 binding preference transmitted efficiently, a single amino acid mutation on HA resulted in a mixed α2-3 sialylated glycan (α2-3)/α2-6 binding virus (NY18) that transmitted inefficiently. To define the biochemical basis for the observed differences in virus transmission, in this study, we have developed an approach to quantify the multivalent HA-glycan interactions. Analysis of the molecular HA-glycan contacts showed subtle changes resulting from the single amino acid variations between SC18 and NY18. The effect of these changes on glycan binding is amplified by multivalency, resulting in quantitative differences in their long α2-6 glycan binding affinities. Furthermore, these differences are also reflected in the markedly distinct binding pattern of SC18 and NY18 HA to the physiological glycans present in human upper respiratory tissues. Thus, the dramatic lower binding affinity of NY18 to long α2-6 glycans, as against a mixed α2-3/6 binding, correlates with its inefficient transmission. In summary, this study establishes a quantitative biochemical correlate for influenza A virus transmission.
机译：人类对A型流感病毒的适应性受病毒表面血凝素（HA）与人类上呼吸道组织上长（链长）α2-6唾液酸化聚糖（α2-6）受体的结合特异性的严格控制。一项最新研究表明，尽管具有α2-6结合偏好的1918年H1N1大流行病毒A /南卡罗来纳州/ 1/1918（SC18）有效地传播，但HA上的单个氨基酸突变导致混合了α2-3唾液酸化聚糖（无法有效传播的α2-3）/α2-6结合病毒（NY18）。为了定义观察到的病毒传播差异的生化基础，在这项研究中，我们开发了一种量化多价HA-聚糖相互作用的方法。分子HA-聚糖接触分析表明，SC18和NY18之间的单个氨基酸变异导致细微变化。这些变化对聚糖结合的影响通过多价放大，导致它们的长α2-6聚糖结合亲和力存在定量差异。此外，这些差异还反映在SC18和NY18 HA与人类上呼吸道组织中存在的生理聚糖明显不同的结合模式上。因此，相对于混合的α2-3/ 6结合，NY18对长α2-6聚糖的显着较低的结合亲和力与其低效的传递有关。总之，本研究建立了甲型流感病毒传播的定量生化相关性。

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