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

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
eLife | 2019

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.

Pubmed ID: 31452511

Research resources used in this publication

None found

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Antibodies used in this publication

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Associated grants

  • Agency: NIH HHS, United States
    Id: R01 AI108686
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI108686
  • Agency: NIH HHS, United States
    Id: U54GM111274
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI127893
  • Agency: NIH HHS, United States
    Id: HHSN272201400005C
  • Agency: NIH HHS, United States
    Id: F30 AI136326
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM119774
  • Agency: NIH HHS, United States
    Id: R35 GM119774
  • Agency: NIH HHS, United States
    Id: R01 AI113047
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI113047
  • Agency: NIAID NIH HHS, United States
    Id: P01 AI097092
  • Agency: NIH HHS, United States
    Id: U19 AI117891
  • Agency: NIH HHS, United States
    Id: R01 AI141707
  • Agency: NIH HHS, United States
    Id: S10 OD020069
  • Agency: NIAID NIH HHS, United States
    Id: F30 AI136326
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007266

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GenBank (tool)

RRID:SCR_002760

NIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.

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WI (tool)

RRID:RGD_13508588

Rattus norvegicus with name WI from RGD.

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