IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission
- Medical Center University of Freiburg, Germany
- Aarhus University, Denmark
- 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
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
- 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
- Received: November 5, 2017
- Accepted: April 11, 2018
- Accepted Manuscript published: April 13, 2018 (version 1)
- 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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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
