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Elife. 2019 Aug 27;8. pii: e49324. doi: 10.7554/eLife.49324.

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

Author information

1
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
2
Department of Genome Sciences, University of Washington, Seattle, United States.
3
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.
4
Department of Biological Sciences, University of Southern California, Los Angeles, United States.
5
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, United States.
6
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
7
WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
8
Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, United States.
9
Howard Hughes Medical Institute, Seattle, United States.

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.

KEYWORDS:

antigenic drift; deep mutational scanning; evolutionary biology; hemagglutinin; human; infectious disease; influenza virus; microbiology; mutational antigenic profiling; virus

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