Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing.
Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing.
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作者：
Wang Y;Lei R;Nourmohammad A;Wu NC
H3N2病毒的神经氨酸酶（NA）作为流感病毒的主要抗原之一，在持续的免疫压力下经历了50多年的广泛进化。虽然NA最近已成为一个有效的疫苗靶点，NA的抗原性进化的生物物理限制仍然在很大程度上难以捉摸。在这里，我们应用组合诱变和下一代测序来表征六种不同的人类H3N2毒株中NA抗原区域的局部适应性景观，这些毒株相隔约10年分离。菌株间的局部适应度景观具有很好的相关性，并且两两上位性是高度保守的。我们的分析进一步表明，局部净电荷控制在这个抗原区域的成对上位性。此外，我们表明，在这个抗原区域的残基协同进化与电荷状态之间的成对上位性。总体而言，这项研究表明了量化上位性和潜在的生物物理约束建立流感演变模型的重要性。
As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has recently emerged as an effective vaccine target, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region is correlated with the pairwise epistasis between charge states. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a model of influenza evolution.