IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission

  1. Jonas Klinkhammer
  2. Daniel Schnepf
  3. Liang Ye
  4. Marilena Schwaderlapp
  5. Hans Henrik Gad
  6. Rune Hartmann
  7. Dominique Garcin
  8. Tanel Mahlakõiv
  9. Peter Staeheli  Is a corresponding author
  1. Medical Center University of Freiburg, Germany
  2. Aarhus University, Denmark
  3. University of Geneva, Switzerland

Abstract

Host factors restricting the transmission of respiratory viruses are poorly characterized. We analyzed the contribution of type I and type III interferon (IFN) using a mouse model in which the virus is selectively administered to the upper airways, mimicking a natural respiratory virus infection. Mice lacking functional IFN-λ receptors (Ifnlr1-/-) no longer restricted virus dissemination from the upper airways to the lungs. Ifnlr1-/- mice shed significantly more infectious virus particles via the nostrils and transmitted the virus much more efficiently to naïve contacts compared with wild-type mice or mice lacking functional type I IFN receptors. Prophylactic treatment with IFN-α or IFN-λ inhibited initial virus replication in all parts of the respiratory tract, but only IFN-λ conferred long-lasting antiviral protection in the upper airways and blocked virus transmission. Thus, IFN-λ has a decisive and non-redundant function in the upper airways that greatly limits transmission of respiratory viruses to naïve contacts.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jonas Klinkhammer

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel Schnepf

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Liang Ye

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Marilena Schwaderlapp

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Hans Henrik Gad

    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8449-1115
  6. Rune Hartmann

    Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  7. Dominique Garcin

    Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1556-897X
  8. Tanel Mahlakõiv

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Peter Staeheli

    Institute of Virology, Medical Center University of Freiburg, Freiburg, Germany
    For correspondence
    peter.staeheli@uniklinik-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7057-6177

Funding

Deutsche Forschungsgemeinschaft

  • Peter Staeheli

Novo Nordisk

  • Rune Hartmann

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  • Dominique Garcin

European Commission

  • Peter Staeheli

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

Reviewing Editor

  1. Viviana Simon, Icahn School of Medicine at Mount Sinai, United States

Ethics

Animal experimentation: Animals were handled in accordance with guidelines of the Federation for Laboratory Animal Science Associations and the national animal welfare body. Animal experiments were performed in compliance with the German animal protection laws and were approved by the university's animal welfare committee (Regierungspräsidium Freiburg; permit G-15/59).

Version history

  1. Received: November 5, 2017
  2. Accepted: April 11, 2018
  3. Accepted Manuscript published: April 13, 2018 (version 1)
  4. Version of Record published: May 15, 2018 (version 2)

Copyright

© 2018, Klinkhammer 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. Jonas Klinkhammer
  2. Daniel Schnepf
  3. Liang Ye
  4. Marilena Schwaderlapp
  5. Hans Henrik Gad
  6. Rune Hartmann
  7. Dominique Garcin
  8. Tanel Mahlakõiv
  9. Peter Staeheli
(2018)
IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission
eLife 7:e33354.
https://doi.org/10.7554/eLife.33354

Share this article

https://doi.org/10.7554/eLife.33354

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