Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
Lee, Juhye M.; Eguia, Rachel; Zost, Seth J.; Choudhary, Saket; Wilson, Patrick C.; Bedford, Trevor; Stevens-Ayers, Terry; Boeckh, Michael; Hurt, Aeron C.; Lakdawala, Seema S.; Hensley, Scott E.; Bloom, Jesse D.
2019
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Abstract

A longstanding question is how influenza virus evolves to escape human immunity, which is polyclonal and can target many distinct epitopes. Here, we map how all amino-acid mutations to influenza's major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets that have been infected just once with a defined viral strain. Our results show how different single mutations help influenza virus escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.

Details

Title
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
Author
Lee, Juhye M. : Fred Hutchinson Cancer Research Center
Eguia, Rachel : Fred Hutchinson Cancer Research Center
Zost, Seth J. : University of Pennsylvania : (https://orcid.org/0000-0001-6712-5076)
Choudhary, Saket : University of Southern California : (https://orcid.org/0000-0001-5202-7633)
Wilson, Patrick C. : University of Chicago
Bedford, Trevor : Fred Hutchinson Cancer Research Center
Stevens-Ayers, Terry : Fred Hutchinson Cancer Research Center
Boeckh, Michael : Fred Hutchinson Cancer Research Center
Hurt, Aeron C. : Peter Doherty Institute for Infection and Immunity
Lakdawala, Seema S. : University of Pittsburgh : (https://orcid.org/0000-0002-7679-2150)
Hensley, Scott E. : University of Pennsylvania
Bloom, Jesse D. : Fred Hutchinson Cancer Research Center : (https://orcid.org/0000-0003-1267-3408)
Content Type
Article
Published in
eLife
Keywords
Identifier(s)
DOI: https://doi.org/10.7554/eLife.49324
Data availability statement

All computer code and processed data are on GitHub at https://github.com/jbloomlab/map_flu_serum_Perth2009_H3_HA (copy archived at https://github.com/elifesciences-publications/map_flu_serum_Perth2009_H3_HA). Deep sequencing data are on the Sequence Read Archive under BioSample accession numbers SAMN10183083 and SAMN11310465 (viral libraries selected with monoclonal antibodies), SAMN10183146 (monoclonal antibody selection controls), SAMN11310372 (viral libraries selected with human sera), SAMN11310371 (viral libraries selected with ferret sera), SAMN11341221 (viral libraries selected with human sera spiked with monoclonal antibody), and SAMN11310373 (serum selection controls).

The following data sets were generated:

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN10183083. Mutational antigenic profiling of antibodies. https://www.ncbi.nlm.nih.gov/biosample/SAMN10183083

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN11310465. Mutational antigenic profiling of antibodies. https://www.ncbi.nlm.nih.gov/biosample/SAMN11310465

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN10183146. Mutational antigenic profiling antibody controls. https://www.ncbi.nlm.nih.gov/biosample/SAMN10183146

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN11310372. Mutational antigenic profiling of human sera. https://www.ncbi.nlm.nih.gov/biosample/SAMN11310372

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN11310371. Mutational antigenic profiling of ferret sera. https://www.ncbi.nlm.nih.gov/biosample/SAMN11310371

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt A Lakdawala SS Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN11341221. Mutational antigenic profiling of antibody spike in. https://www.ncbi.nlm.nih.gov/biosample/SAMN11341221

Lee JM Eguia R Zost SJ Choudhyar S Wilson PC Bedford T Stevens-Ayers T Bo eckh M Hurt ALakdawala SS. Hensley SE Bloom JD (2019) Sequence Read Archive ID SAMN11310373. Mutational antigenic profiling sera controls. https://www.ncbi.nlm.nih.gov/biosample/SAMN11310373

Funding Information
National Institutes of Health, R01 AI127893
National Institutes of Health, R01 AI141707
National Institutes of Health, R01 AI113047
National Institutes of Health, R01 AI108686
National Institutes of Health, HHSN272201400005C
Burroughs Wellcome Fund
National Institutes of Health, F30 AI136326
National Institutes of Health, U54GM111274
Pew Charitable Trusts
National Institutes of Health, R35 GM119774
National Institutes of Health, U19 AI117891
Howard Hughes Medical Institute
Publication Date
2019-08-27
Language
English
Copyright Statement

© 2019, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Licensing
Record Appears in
Biological Sciences Division > Medicine
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Record Created
2023-11-28

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