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Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin.


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.

SUBMITTER: Lee JM 

PROVIDER: S-EPMC6711711 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin.

Lee Juhye M JM   Eguia Rachel R   Zost Seth J SJ   Choudhary Saket S   Wilson Patrick C PC   Bedford Trevor T   Stevens-Ayers Terry T   Boeckh Michael M   Hurt Aeron C AC   Lakdawala Seema S SS   Hensley Scott E SE   Bloom Jesse D JD  

eLife 20190827


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 indi  ...[more]

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