title: Antiviral activity of lambda interferon in chickens.
abstract: Interferons (IFNs) are essential components of the antiviral defense system of vertebrates. In mammals, functional receptors for type III IFN (lambda interferon [IFN-λ]) are found mainly on epithelial cells, and IFN-λ was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-λ plays a similar role in birds, we produced recombinant chicken IFN-λ (chIFN-λ) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-λ. We could demonstrate that chIFN-λ markedly inhibited replication of various virus strains, including highly pathogenic influenza A viruses, in ovo and in vivo, as well as in epithelium-rich tissue and cell culture systems. In contrast, chicken fibroblasts responded poorly to chIFN-λ. When applied in vivo to 3-week-old chickens, recombinant chIFN-λ strongly induced the IFN-responsive Mx gene in epithelium-rich organs, such as lungs, tracheas, and intestinal tracts. Correspondingly, these organs were found to express high transcript levels of the putative chIFN-λ receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-λ treatment, indicating that receptor expression determines cell type specificity of IFN-λ action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-λ expression. Our data highlight fundamental similarities between the IFN-λ systems of mammals and birds and suggest that type III IFN might play a role in defending mucosal surfaces against viral intruders in most if not all vertebrates.
authors.affiliation: Institute for Virology, University of Freiburg, Freiburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Reuter
authors.forename: Sebastien
authors.initials: S
authors.lastname: Soubies
authors.forename: Sonja
authors.initials: S
authors.lastname: Härtle
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schusser
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaspers
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Dennis
authors.initials: D
authors.lastname: Rubbenstroth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D060467:Disease Resistance / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005804:Genes, Lethal; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000472:pathogenicity; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity; D005585:Influenza in Birds / Q000188:drug therapy / Q000821:virology; D007372:Interferons / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D018121:Receptors, Cytokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016415:Sequence Alignment; D046509:Tissue Culture Techniques; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D064547:Myxovirus Resistance Proteins; D018121:Receptors, Cytokine; D011994:Recombinant Proteins; C471046:interleukin 28alpha receptor; D007372:Interferons