Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin
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 individua...
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doaj-2119b3de6f684d84a4356f027f1983d82021-05-05T17:52:40ZengeLife Sciences Publications LtdeLife2050-084X2019-08-01810.7554/eLife.49324Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutininJuhye M Lee0Rachel Eguia1Seth J Zost2https://orcid.org/0000-0001-6712-5076Saket Choudhary3https://orcid.org/0000-0001-5202-7633Patrick C Wilson4Trevor Bedford5https://orcid.org/0000-0002-4039-5794Terry Stevens-Ayers6Michael Boeckh7Aeron C Hurt8Seema S Lakdawala9https://orcid.org/0000-0002-7679-2150Scott E Hensley10Jesse D Bloom11https://orcid.org/0000-0003-1267-3408Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Department of Genome Sciences, University of Washington, Seattle, United StatesBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biological Sciences, University of Southern California, Los Angeles, United StatesDepartment of Medicine, Section of Rheumatology, University of Chicago, Chicago, United StatesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesVaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United StatesWHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, AustraliaDepartment of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, United StatesDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States; Department of Genome Sciences, University of Washington, Seattle, United States; Howard Hughes Medical Institute, Seattle, United StatesA 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.https://elifesciences.org/articles/49324influenza virusdeep mutational scanninghemagglutininantigenic driftmutational antigenic profiling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juhye M Lee Rachel Eguia Seth J Zost Saket Choudhary Patrick C Wilson Trevor Bedford Terry Stevens-Ayers Michael Boeckh Aeron C Hurt Seema S Lakdawala Scott E Hensley Jesse D Bloom |
spellingShingle |
Juhye M Lee Rachel Eguia Seth J Zost Saket Choudhary Patrick C Wilson Trevor Bedford Terry Stevens-Ayers Michael Boeckh Aeron C Hurt Seema S Lakdawala Scott E Hensley Jesse D Bloom Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin eLife influenza virus deep mutational scanning hemagglutinin antigenic drift mutational antigenic profiling |
author_facet |
Juhye M Lee Rachel Eguia Seth J Zost Saket Choudhary Patrick C Wilson Trevor Bedford Terry Stevens-Ayers Michael Boeckh Aeron C Hurt Seema S Lakdawala Scott E Hensley Jesse D Bloom |
author_sort |
Juhye M Lee |
title |
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
title_short |
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
title_full |
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
title_fullStr |
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
title_full_unstemmed |
Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
title_sort |
mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-08-01 |
description |
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. |
topic |
influenza virus deep mutational scanning hemagglutinin antigenic drift mutational antigenic profiling |
url |
https://elifesciences.org/articles/49324 |
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