Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing
- University of Illinois at Urbana-Champaign, United States
- University of Washington, United States
Abstract
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.
Data availability
Raw sequencing data have been submitted to the NIH Short Read Archive under accession number: BioProject PRJNA742436. Custom python scripts for analyzing the deep mutational scanning data have been deposited to https://github.com/Wangyiquan95/NA_EPI.
-
Deep mutational scanning of human H3N2 influenza virus NA residues 328, 329, 344, 367, 368, 369, and 370NIH Short Read Archive BioProject, PRJNA742436.
Article and author information
Author details
Armita Nourmohammad
Funding
Deutsche Forschungsgemeinschaft (SFB1310)
- Armita Nourmohammad
Max Planck Society (MPRG funding)
- Armita Nourmohammad
University of Washington (Royalty Research Fund: A153352)
- Armita Nourmohammad
National Institutes of Health (R00 AI139445)
- Nicholas C Wu
National Institutes of Health (DP2 AT011966)
- Nicholas C Wu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing
eLife 10:e72516.
https://doi.org/10.7554/eLife.72516
