Virus-infected cells secrete a broad range of interferon (IFN) subtypes which in turn trigger the synthesis of antiviral factors that confer host resistance. IFN-α , IFN-β and other type I IFNs signal through a common universally expressed cell surface receptor (IFNAR), whereas type III IFN (IFN-λ) uses a distinct cell-type-specific receptor complex (IL28R) for signaling. Using mice lacking functional receptors for IFNAR, IL28R, or both, we have recently shown that IFN-λ contributes to resistance against influenza A viruses (Mordstein et al., PLoS Pathogens 2008). We now present data indicating that IFN-λ also plays an important role in defense against several other human pathogenic viruses infecting the respiratory tract such as influenza B virus, respiratory syncytial virus and SARS coronavirus. These viruses replicated to significantly higher titers in the lung of mice lacking both IFN receptors than in mice with single IFN receptor defects. Interestingly, Lassa fever virus that also infects via the respiratory tract but primarily replicates in the liver was not affected by the IFN-λ receptor defect. We managed to visualize cells expressing functional IL28R complexes in lung and intestinal tract which may account for IFN-λ mediated inhibition of virus replication and shedding.
Mordstein Markus, Neugebauer Eva, Ditt Vanessa, Jessen Birthe, Rieger Toni, Günther Stephan, Wolff Thorsten, Klucher Kevin, Kochs Georg, Ehl Stephan, Michiels Thomas, Drosten Christian, Staeheli Peter, Poster Presentation I