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

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    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.

    OriginalsprogEngelsk
    Artikelnummere33354
    TidsskrifteLife
    Vol/bind7
    Antal sider18
    ISSN2050-084X
    DOI
    StatusUdgivet - 13 apr. 2018

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