Klinkhammer, Jonas
[Author];
Schnepf, Daniel
[Author];
Ye, Liang
[Author];
Schwaderlapp, Marilena
[Author];
Gad, Hans Henrik
[Author];
Hartmann, Rune
[Author];
Garcin, Dominique
[Author];
Mahlakõiv, Tanel
[Author];
Stäheli, Peter
[Author]
IFN-[lambda] prevents influenza virus spread from the upper airways to the lungs and limits virus transmission
Description:
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