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Conserved amino acid markers from past influenza pandemic strains

机译：过去流感大流行毒株的保守氨基酸标记

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Background Finding the amino acid mutations that affect the severity of influenza infections remains an open and challenging problem. Of special interest is better understanding how current circulating influenza strains could evolve into a new pandemic strain. Influenza proteomes from distinct viral phenotype classes were searched for class specific amino acid mutations conserved in past pandemics, using reverse engineered linear classifiers. Results Thirty-four amino acid markers associated with host specificity and high mortality rate were found. Some markers had little impact on distinguishing the functional classes by themselves, however in combination with other mutations they improved class prediction. Pairwise combinations of influenza genomes were checked for reassortment and mutation events needed to acquire the pandemic conserved markers. Evolutionary pathways involving H1N1 human and swine strains mixed with avian strains show the potential to acquire the pandemic markers with a double reassortment and one or two amino acid mutations. Conclusion The small mutation combinations found at multiple protein positions associated with viral phenotype indicate that surveillance tools could monitor genetic variation beyond single point mutations to track influenza strains. Finding that certain strain combinations have the potential to acquire pandemic conserved markers through a limited number of reassortment and mutation events illustrates the potential for reassortment and mutation events to lead to new circulating influenza strains.
机译：背景技术寻找影响流感感染严重程度的氨基酸突变仍然是一个开放而具有挑战性的问题。特别令人感兴趣的是，更好地了解当前流行的流感毒株如何演变为新的大流行毒株。使用反向工程线性分类器，搜索来自不同病毒表型类别的流感蛋白质组，以寻找过去大流行中保守的类别特异性氨基酸突变。结果发现了34种与宿主特异性和高死亡率相关的氨基酸标记。某些标记本身对区分功能类别影响不大，但是与其他突变结合使用时，它们可以改善类别预测。检查流感基因组的成对组合，以获得获得大流行保守标记所需的重配和突变事件。涉及H1N1人和猪品系与禽品系混合的进化途径显示了获得具有双重重排和一个或两个氨基酸突变的大流行标记的潜力。结论在与病毒表型有关的多个蛋白质位置上发现的小突变组合表明，监测工具可以监测单点突变以外的遗传变异，以追踪流感病毒株。发现某些菌株组合具有通过有限数量的重排和突变事件获得大流行保守标记的潜力，这说明了重排和突变事件导致新的流行流感株的潜力。

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