Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

eLife

Yiquan Wang¹  Ruipeng Lei¹  Nicholas C Wu²  Armita Nourmohammad³ 

[1] Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States;Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States;Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, United States;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, United States;Carle Illinois College of Medicine, University of Illinois at Urbana-Champaign, Urbana, United States;Department of Physics, University of Washington, Seattle, United States;Max Planck Institute for Dynamics and Self-Organization, Göttingen, Germany;Fred Hutchinson Cancer Research Center, Seattle, United States;

关键词: influenza;    neuraminidase;    evolution;    epistasis;    combinatorial mutagenesis;    next-generation sequencing;    Influenza virus;   

DOI  :  10.7554/eLife.72516

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY