Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
Department of Physics, University of Washington, Seattle, United States.
Elife. 2021 Dec 8;10:e72516. doi: 10.7554/eLife.72516.
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.
作为主要的流感抗原之一，H3N2 病毒的神经氨酸酶（NA）由于持续的免疫压力而经历了广泛的进化。尽管 NA 最近已成为一种有效的疫苗靶点，但 NA 抗原进化的生物物理限制在很大程度上仍难以捉摸。在这里，我们应用组合诱变和下一代测序来描述在相隔约 10 年分离的六个不同的人类 H3N2 株中 NA 的抗原区域中的局部适应性景观。局部适应性景观在株间很好地相关，并且成对的上位性高度保守。我们的分析进一步表明，局部净电荷控制着这个抗原区域中的成对上位性。此外，我们表明，这个抗原区域中残基的共进化与电荷状态之间的成对上位性相关。总的来说，这项研究表明了量化上位性和潜在的生物物理限制对于建立流感进化模型的重要性。
