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IFN-\u03b1, IFN-\u03b2, and other type I IFN molecules signal through a common, universally expressed cell surface receptor, whereas type III IFN (IFN-\u03bb) uses a distinct cell-type-specific receptor complex for signaling. Using mice lacking functional receptors for type I IFN, type III IFN, or both, we found that IFN-\u03bb plays an important role in the defense against several human pathogens that infect the respiratory tract, such as influenza A virus, influenza B virus, respiratory syncytial virus, human metapneumovirus, and severe acute respiratory syndrome (SARS) coronavirus. These viruses were more pathogenic and replicated to higher titers in the lungs of mice lacking both IFN receptors than in mice with single IFN receptor defects. In contrast, Lassa fever virus, which infects via the respiratory tract but primarily replicates in the liver, was not influenced by the IFN-\u03bb receptor defect. Careful analysis revealed that expression of functional IFN-\u03bb receptor complexes in the lung and intestinal tract is restricted to epithelial cells and a few other, undefined cell types. Interestingly, we found that SARS coronavirus was present in feces from infected mice lacking receptors for both type I and type III IFN but not in those from mice lacking single receptors, supporting the view that IFN-\u03bb contributes to the control of viral infections in epithelial cells of both respiratory and gastrointestinal tracts.<\/jats:p>","DOI":"10.1128\/jvi.00272-10","type":"journal-article","created":{"date-parts":[[2010,3,24]],"date-time":"2010-03-24T23:09:29Z","timestamp":1269472169000},"page":"5670-5677","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":415,"title":["Lambda Interferon Renders Epithelial Cells of the Respiratory and Gastrointestinal Tracts Resistant to Viral Infections"],"prefix":"10.1128","volume":"84","author":[{"given":"Markus","family":"Mordstein","sequence":"first","affiliation":[{"name":"Department of Virology"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), 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