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

Abstract
Data availability
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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.

The following data sets were generated

1. Wang Y
2. Wu NC
(2021) Deep mutational scanning of human H3N2 influenza virus NA residues 328, 329, 344, 367, 368, 369, and 370
NIH Short Read Archive BioProject, PRJNA742436.

https://www.ncbi.nlm.nih.gov/bioproject/742436

Article and author information

Author details

Yiquan Wang

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-1954-9808
Ruipeng Lei

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4652-3400
Armita Nourmohammad

Department of Physics, University of Washington, Seattle, United States

Competing interests
Armita Nourmohammad, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0002-6245-3553
Nicholas C Wu

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States

For correspondence
nicwu@illinois.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-9078-6697

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

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.