Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape.

Nature Communications
Nicholas C WuIan A Wilson

Abstract

Antigenic drift of influenza virus hemagglutinin (HA) is enabled by facile evolvability. However, HA antigenic site B, which has become immunodominant in recent human H3N2 influenza viruses, is also evolutionarily constrained by its involvement in receptor binding. Here, we employ deep mutational scanning to probe the local fitness landscape of HA antigenic site B in six different human H3N2 strains spanning from 1968 to 2016. We observe that the fitness landscape of HA antigenic site B can be very different between strains. Sequence variants that exhibit high fitness in one strain can be deleterious in another, indicating that the evolutionary constraints of antigenic site B have changed over time. Structural analysis suggests that the local fitness landscape of antigenic site B can be reshaped by natural mutations via modulation of the receptor-binding mode. Overall, these findings elucidate how influenza virus continues to explore new antigenic space despite strong functional constraints.

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Citations

Sep 26, 2020·Viruses·Nicholas C Wu, Ian A Wilson
Oct 11, 2020·Vaccines·Nongluk Sriwilaijaroen, Yasuo Suzuki
Nov 5, 2020·The Journal of Biological Chemistry·Andrew J Thompson, James C Paulson
Feb 2, 2021·Frontiers in Microbiology·Alessandra RomanoFrancesco Gonella
Jan 16, 2021·Science·Brian HieBryan Bryson
Mar 23, 2021·PLoS Pathogens·Chang-Chun D LeeIan A Wilson
Apr 27, 2021·Frontiers in Molecular Biosciences·Krishna K Narayanan, Erik Procko
Jun 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Daniel J GoetschiusSusan L Hafenstein
Jun 3, 2021·Viruses·Thomas D Burton, Nicholas S Eyre
Jul 10, 2021·Cell Host & Microbe·Will FischerBette Korber

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Methods Mentioned

BETA
PCR
transfection
Illumina sequencing

Software Mentioned

BioPython
Refmac5
mathop
Coot

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