IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission
Jonas Klinkhammer,
Daniel Schnepf,
Liang Ye,
Marilena Schwaderlapp,
Hans Henrik Gad,
Rune Hartmann,
Dominique Garcin,
Tanel Mahlakõiv,
Peter Staeheli
Affiliations
Jonas Klinkhammer
Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany; MOTI-VATE Graduate School, Medical Center, University of Freiburg, Freiburg, Germany
Daniel Schnepf
Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany; 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
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.
