Suzuki Yoshiyuki
Graduate School of Natural Sciences, Nagoya City University.
Genes Genet Syst. 2013;88(4):225-32. doi: 10.1266/ggs.88.225.
Influenza A virus continues to pose a threat to public health. Since this virus can evolve escape mutants rapidly, it is desirable to predict the antigenic evolution for developing effective vaccines. Although empirical methods have been proposed and reported to predict the antigenic evolution more or less accurately, they did not provide much insight into the effects of unobserved mutations and the mechanisms of antigenic evolution. Here a theoretical method was introduced to predict the antigenic evolution of H3N2 human influenza A virus by evaluating de novo mutations through estimating the antigenic distance. The antigenic distance defined with the hemagglutination inhibition (HI) titer was estimated with antigenic models taking into account the volume, isoelectric point, relative solvent accessibility, and distances from receptor-binding sites (RBS) and N-linked glycosylation sites (NGS) for amino acids in hemagglutinin 1 (HA1). When the best model with the optimized parameter values was used to predict the antigenic evolution for the dominant strains, the prediction accuracy was relatively low. However, there appeared to be an overall tendency that the amino acid sites with larger potential net effect on antigenicity were more likely to evolve and the amino acid changes with larger potential effect were more likely to take place, suggesting that natural selection may operate to enhance the antigenic evolution of H3N2 human influenza A virus.
甲型流感病毒继续对公众健康构成威胁。由于这种病毒能够迅速进化出逃逸突变体，因此预测其抗原进化对于开发有效的疫苗很有必要。尽管已经提出并报道了一些经验方法来或多或少准确地预测抗原进化，但它们并未深入了解未观察到的突变的影响以及抗原进化的机制。在此，引入了一种理论方法，通过估计抗原距离来评估从头突变，从而预测H3N2甲型人流感病毒的抗原进化。利用考虑了血凝素1（HA1）中氨基酸的体积、等电点、相对溶剂可及性以及与受体结合位点（RBS）和N-连接糖基化位点（NGS）的距离的抗原模型，估计了用血凝抑制（HI）效价定义的抗原距离。当使用具有优化参数值的最佳模型来预测优势毒株的抗原进化时，预测准确性相对较低。然而，似乎存在一种总体趋势，即对抗原性具有较大潜在净效应的氨基酸位点更有可能进化，而具有较大潜在效应的氨基酸变化更有可能发生，这表明自然选择可能在促进H3N2甲型人流感病毒的抗原进化中起作用。
