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

Yiquan Wang, Ruipeng Lei, Armita Nourmohammad, Nicholas C. Wu

Research output: Contribution to journalArticlepeer-review

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 biophys-ical constraint for building a model of influenza evolution.

Original languageEnglish (US)
Article numbere72516
JournaleLife
Volume10
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

Fingerprint

Dive into the research topics of 'Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing'. Together they form a unique fingerprint.

Cite this