TY - JOUR TI - IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission AU - Klinkhammer, Jonas AU - Schnepf, Daniel AU - Ye, Liang AU - Schwaderlapp, Marilena AU - Gad, Hans Henrik AU - Hartmann, Rune AU - Garcin, Dominique AU - Mahlakõiv, Tanel AU - Staeheli, Peter A2 - Simon, Viviana VL - 7 PY - 2018 DA - 2018/04/13 SP - e33354 C1 - eLife 2018;7:e33354 DO - 10.7554/eLife.33354 UR - https://doi.org/10.7554/eLife.33354 AB - 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. KW - Influenza virus KW - interferons KW - transmission KW - respiratory tract JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -