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-?]) are found mainly on epithelial cells, and IFN-? was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-? plays a similar role in birds, we produced recombinant chicken IFN-? (chIFN-?) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-?. We could demonstrate that chIFN-? 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-?. When applied in vivo to 3-week-old chickens, recombinant chIFN-? 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-? receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-? treatment, indicating that receptor expression determines cell type specificity of IFN-? action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-? expression. Our data highlight fundamental similarities between the IFN-? 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.

SUBMITTER: Reuter A 

PROVIDER: S-EPMC3958073 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature