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.
Highlights
Influenza and other respiratory viruses are readily transmitted in community settings
Respiratory viruses enter the human body via the upper respiratory tract, and the majority of acute respiratory viral infections in humans are confined to the upper airways (Cotton et al, 2008)
IFN-l has previously been recognized as an important component of the innate immune system that limits the replication of viruses infecting epithelial cells of the intestinal tract (Lazear et al, 2015; Wack et al, 2015)
Summary
Influenza and other respiratory viruses are readily transmitted in community settings. The resulting infection chains and concomitant diseases represent an enormous economic and public health burden (Osterhaus et al, 2015). At present, it is largely unknown if and how the innate immune response influences virus transmission efficacy. The members of the type III IFN family (IFN-l) bind to a different receptor complex (IFN-l receptor; IFNLR), which is highly expressed on epithelial cells
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