Stochastic processes constrain the within and between host evolution of influenza virus

Abstract

The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1-2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided. All sequence reads have been deposited to NCBI's BioProject under accession number PRJNA412631.

The following data sets were generated

Article and author information

Author details

  1. John T McCrone

    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9846-8917
  2. Robert J Woods

    Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Emily T Martin

    Department of Epidemiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ryan E Malosh

    Department of Epidemiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3546-5935
  5. Arnold S Monto

    Department of Epidemiology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Adam S Lauring

    Department of Microbiology and Immunology, University of Michigan, Ann Arbor, United States
    For correspondence
    alauring@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2906-8335

Funding

Doris Duke Charitable Foundation (CSDA 2013105)

  • Adam S Lauring

National Institute of Allergy and Infectious Diseases (R01 AI118886)

  • Adam S Lauring

National Institute of General Medical Sciences (T32 GM007544)

  • John T McCrone

Centers for Disease Control and Prevention (U01 IP00474)

  • Arnold S Monto

National Institute of Allergy and Infectious Diseases (K08 AI119182)

  • Robert J Woods

National Institute of Allergy and Infectious Diseases (R01 AI097150)

  • Arnold S Monto

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved by the Institutional Review Board of the University of Michigan Medical School. Adults provided written informed consent for participation for themselves and their children; children 7-17 years provided oral assent.

Reviewing Editor

  1. Richard A Neher, University of Basel, Switzerland

Publication history

  1. Received: February 15, 2018
  2. Accepted: April 18, 2018
  3. Accepted Manuscript published: April 23, 2018 (version 1)
  4. Version of Record published: May 3, 2018 (version 2)
  5. Version of Record updated: June 29, 2018 (version 3)

Copyright

© 2018, McCrone et al.

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

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  1. John T McCrone
  2. Robert J Woods
  3. Emily T Martin
  4. Ryan E Malosh
  5. Arnold S Monto
  6. Adam S Lauring
(2018)
Stochastic processes constrain the within and between host evolution of influenza virus
eLife 7:e35962.
https://doi.org/10.7554/eLife.35962
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