Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children

  1. Alvin X Han  Is a corresponding author
  2. Zandra C Felix Garza
  3. Matthijs RA Welkers
  4. René M Vigeveno
  5. Nhu Duong Tran
  6. Thi Quynh Mai Le
  7. Thai Pham Quang
  8. Dinh Thoang Dang
  9. Thi Ngoc Anh Tran
  10. Manh Tuan Ha
  11. Thanh Hung Nguyen
  12. Quoc Thinh Le
  13. Thanh Hai Le
  14. Thi Bich Ngoc Hoang
  15. Kulkanya Chokephaibulkit
  16. Pilaipan Puthavathana
  17. Van Vinh Chau Nguyen
  18. My Ngoc Nghiem
  19. Van Kinh Nguyen
  20. Tuyet Trinh Dao
  21. Tinh Hien Tran
  22. Heiman FL Wertheim
  23. Peter W Horby
  24. Annette Fox
  25. H Rogier van Doorn
  26. Dirk Eggink
  27. Menno D de Jong
  28. Colin A Russell  Is a corresponding author
  1. Amsterdam University Medical Center, Netherlands
  2. National Institute of Hygiene and Epidemiology, Viet Nam
  3. National Institute Of Hygiene And Epidemiology, Viet Nam
  4. Ha Nam Centre for Disease Control, Viet Nam
  5. Children's Hospital 2, Viet Nam
  6. Children's Hospital 1, Viet Nam
  7. Vietnam National Children's Hospital, Viet Nam
  8. Mahidol University, Thailand
  9. Hospital for Tropical Diseases, Viet Nam
  10. National Hospital for Tropical Diseases, Viet Nam
  11. Radboud University, Netherlands
  12. University of Oxford, United Kingdom
  13. University of Melbourne, Australia

Abstract

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analysed the within-host evolution of 82 longitudinally-sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titres decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.

Data availability

All raw sequence data have been deposited at NCBI sequence read archive under BioProject Accession number PRJNA722099. All custom Python code and Jupyter notebooks to reproduce the analyses in this paper are available online: https://github.com/AMC-LAEB/Within_Host_H3vH1.

The following data sets were generated

Article and author information

Author details

  1. Alvin X Han

    Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    For correspondence
    x.han@amsterdamumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6281-8498
  2. Zandra C Felix Garza

    Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7262-2165
  3. Matthijs RA Welkers

    Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2982-0278
  4. René M Vigeveno

    Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Nhu Duong Tran

    -, National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  6. Thi Quynh Mai Le

    -, National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  7. Thai Pham Quang

    Communicable diseases Control and Prevention, National Institute Of Hygiene And Epidemiology, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3796-6162
  8. Dinh Thoang Dang

    -, Ha Nam Centre for Disease Control, Ha Nam, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  9. Thi Ngoc Anh Tran

    -, Children's Hospital 2, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  10. Manh Tuan Ha

    -, Children's Hospital 2, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  11. Thanh Hung Nguyen

    -, Children's Hospital 1, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  12. Quoc Thinh Le

    -, Children's Hospital 1, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  13. Thanh Hai Le

    -, Vietnam National Children's Hospital, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  14. Thi Bich Ngoc Hoang

    -, Vietnam National Children's Hospital, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  15. Kulkanya Chokephaibulkit

    Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  16. Pilaipan Puthavathana

    Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  17. Van Vinh Chau Nguyen

    -, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  18. My Ngoc Nghiem

    -, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  19. Van Kinh Nguyen

    -, National Hospital for Tropical Diseases, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  20. Tuyet Trinh Dao

    -, National Hospital for Tropical Diseases, Hanoi, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  21. Tinh Hien Tran

    -, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
    Competing interests
    The authors declare that no competing interests exist.
  22. Heiman FL Wertheim

    Radboud Medical Centre, Radboud University, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  23. Peter W Horby

    Epidemic Diseases Research Group, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  24. Annette Fox

    Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0565-7146
  25. H Rogier van Doorn

    Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  26. Dirk Eggink

    Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  27. Menno D de Jong

    Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  28. Colin A Russell

    Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology & Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
    For correspondence
    c.a.russell@amsterdamumc.nl
    Competing interests
    The authors declare that no competing interests exist.

Funding

H2020 European Research Council (818353)

  • Alvin X Han
  • Zandra C Felix Garza
  • Colin A Russell

National Institute of Allergy and Infectious Diseases (N01-A0-50042)

  • Matthijs RA Welkers
  • René M Vigeveno
  • Nhu Duong Tran
  • Thi Quynh Mai Le
  • Thai Pham Quang
  • Dinh Thoang Dang
  • Thi Ngoc Anh Tran
  • Manh Tuan Ha
  • Thanh Hung Nguyen
  • Quoc Thinh Le
  • Thanh Hai Le
  • Thi Bich Ngoc Hoang
  • Kulkanya Chokephaibulkit
  • Pilaipan Puthavathana
  • Van Vinh Chau Nguyen
  • My Ngoc Nghiem
  • Van Kinh Nguyen
  • Tuyet Trinh Dao
  • Tinh Hien Tran
  • Heiman FL Wertheim
  • Peter W Horby
  • Annette Fox
  • H Rogier van Doorn
  • Dirk Eggink
  • Menno D de Jong

National Institutes of Health (HHSN272200500042C)

  • Matthijs RA Welkers
  • René M Vigeveno
  • Nhu Duong Tran
  • Thi Quynh Mai Le
  • Thai Pham Quang
  • Dinh Thoang Dang
  • Thi Ngoc Anh Tran
  • Manh Tuan Ha
  • Thanh Hung Nguyen
  • Quoc Thinh Le
  • Thanh Hai Le
  • Thi Bich Ngoc Hoang
  • Kulkanya Chokephaibulkit
  • Pilaipan Puthavathana
  • Van Vinh Chau Nguyen
  • My Ngoc Nghiem
  • Van Kinh Nguyen
  • Tuyet Trinh Dao
  • Tinh Hien Tran
  • Heiman FL Wertheim
  • Peter W Horby
  • Annette Fox
  • H Rogier van Doorn
  • Dirk Eggink
  • Menno D de Jong

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

Ethics

Human subjects: The Institutional Review Board of all hospitals, the National Institute of Allergy and Infectious Diseases, and the Oxford Tropical Research Ethics Committee approved the study. Written informed consent was given by all patients (or proxies).

Reviewing Editor

  1. Sarah E Cobey, University of Chicago, United States

Publication history

  1. Received: March 30, 2021
  2. Accepted: August 2, 2021
  3. Accepted Manuscript published: August 3, 2021 (version 1)
  4. Version of Record published: August 23, 2021 (version 2)

Copyright

© 2021, Han 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. Alvin X Han
  2. Zandra C Felix Garza
  3. Matthijs RA Welkers
  4. René M Vigeveno
  5. Nhu Duong Tran
  6. Thi Quynh Mai Le
  7. Thai Pham Quang
  8. Dinh Thoang Dang
  9. Thi Ngoc Anh Tran
  10. Manh Tuan Ha
  11. Thanh Hung Nguyen
  12. Quoc Thinh Le
  13. Thanh Hai Le
  14. Thi Bich Ngoc Hoang
  15. Kulkanya Chokephaibulkit
  16. Pilaipan Puthavathana
  17. Van Vinh Chau Nguyen
  18. My Ngoc Nghiem
  19. Van Kinh Nguyen
  20. Tuyet Trinh Dao
  21. Tinh Hien Tran
  22. Heiman FL Wertheim
  23. Peter W Horby
  24. Annette Fox
  25. H Rogier van Doorn
  26. Dirk Eggink
  27. Menno D de Jong
  28. Colin A Russell
(2021)
Within-host evolutionary dynamics of seasonal and pandemic human influenza A viruses in young children
eLife 10:e68917.
https://doi.org/10.7554/eLife.68917
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