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

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  • Jonas Klinkhammer, MOTI-VATE Graduate School, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Daniel Schnepf, Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Freiburg, Germany.
  • ,
  • Liang Ye, Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Marilena Schwaderlapp, Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Hans Henrik Gad
  • Rune Hartmann
  • Dominique Garcin, Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
  • ,
  • Tanel Mahlakõiv, Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Peter Staeheli, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine Medical Center, Faculty of Medicine, University of Freiburg, Heiliggeiststrasse 1, 79106, Freiburg, Germany.

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.

Original languageEnglish
Article numbere33354
JournaleLife
Volume7
Number of pages18
ISSN2050-084X
DOIs
Publication statusPublished - 13 Apr 2018

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