The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability.
The hemagglutinin of the influenza A(H1N1)pdm09 is mutating towards stability.
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DOI：
10.2147/aabc.s68934
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发表时间：
2014-01-01
期刊：
影响因子：
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通讯作者：
Ribas-Aparicio, Rosa Maria
中科院分区：
文献类型：
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作者：
Castelan-Vega, Juan A;Magana-Hernandez, Anastasia;Ribas-Aparicio, Rosa Maria
上一次甲型流感大流行为研究甲型H1N1流感pdm09病毒适应人类宿主提供了一个极好的机会。特别是，由于从大流行开始到目前为止从分离株中提取的序列可用，我们可以监测随着病毒在世界范围内传播并成为H1N1主要毒株时血凝素(HA)中发生的氨基酸变化。HA对病毒感染至关重要，因为它与唾液酸化的细胞受体结合，并介导细胞膜和病毒膜的融合；由于与HA结合的抗体可能会阻止病毒进入细胞，这种蛋白受到很高的选择压力。对2009年至今分离的甲型H1N1流感病毒的多个序列进行比对分析，使我们能够发现随着疫情的进展，氨基酸发生了积极的变化。我们发现了9个流行的变化：HA1亚基D104N、K166Q、S188T、S206T、A259T和K285E；以及HA2亚基E47K、S124N和E172K。这些改变大多位于链间和链内相互作用的区域，只有两个(K166Q和S188T)位于已知的抗原位点。我们得出结论，对HA施加选择性压力的目的是改善其功能，从而提高病毒的适合性，而不是为了避免免疫识别。
The last influenza A pandemic provided an excellent opportunity to study the adaptation of the influenza A(H1N1)pdm09 virus to the human host. Particularly, due to the availability of sequences taken from isolates since the beginning of the pandemic until date, we could monitor amino acid changes that occurred in the hemagglutinin (HA) as the virus spread worldwide and became the dominant H1N1 strain. HA is crucial to viral infection because it binds to sialidated cell-receptors and mediates fusion of cell and viral membranes; because antibodies that bind to HA may block virus entry to the cell, this protein is subjected to high selective pressure. Multiple alignment analysis of sequences of the HA from isolates taken since 2009 to date allowed us to find amino acid changes that were positively selected as the pandemic progressed. We found nine changes that became prevalent: HA1 subunits D104N, K166Q, S188T, S206T, A259T, and K285E; and HA2 subunits E47K, S124N, and E172K. Most of these changes were located in areas involved in inter- and intrachain interactions, while only two (K166Q and S188T) were located in known antigenic sites. We conclude that selective pressure on HA was aimed to improve its functionality and hence virus fitness, rather than at avoidance of immune recognition.