BACKGROUND: Interferon regulatory factors (IRFs) are a family of transcription factors with important functions in immunity. The genomes of most vertebrates encode ten IRF genes. IRF3 and IRF9 have key roles in interferon (IFN) induction and signaling. Most of our knowledge about the IFN pathways originates from the study of the mammalian IFN system, and the description of the corresponding avian components is not as complete. Both IRF3 and IRF9 were considered missing from the chicken genome and from the genomes of other avian species. RESULTS: Here we describe multiple avian IRF3 and IRF9 genes, all with difficult GC-rich sequence context that prevented their earlier characterization. IRF3 orthologs are narrowly distributed and are present in the avian infraclass Palaeognathae. In contrast, IRF9 orthologs were found in most avian species, with the exception of the order Galliformes. In about half of the avian orders, IRF9 was located in noncanonical chromosomal positions, indicating past translocations. Phylogenetic analysis confirmed the correct orthology of all newly described IRFs. We further performed experiments using duck IRF9, confirming its role in the IFN pathway. IRF9 knockout in duck fibroblasts decreases the induction of IFN-stimulated genes (ISGs). Full induction of ISGs in duck cells requires both an intact IRF9 and a canonical IFN-stimulated response element. Lastly, intact IRF9 is needed for IFN-mediated protection of duck cells against the vesicular stomatitis virus-induced cytopathicity. CONCLUSIONS: The identification of avian IRFs fills an important gap in our understanding of avian immunology and brings new questions related to the evolution of the IRF family.

• Keywords
• Avian genome, Gene loss, Interferon regulatory factors, Interferon signaling,
• MeSH
• Phylogeny MeSH
• Interferon Regulatory Factors * genetics   metabolism   MeSH
• Interferon Regulatory Factor-3 * genetics   metabolism   MeSH
• Interferon-Stimulated Gene Factor 3, gamma Subunit * genetics   metabolism   MeSH
• Ducks genetics   MeSH
• Chickens genetics   MeSH
• Avian Proteins * genetics   metabolism   MeSH
• Birds * genetics   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Interferon Regulatory Factors * MeSH
• Interferon Regulatory Factor-3 * MeSH
• Interferon-Stimulated Gene Factor 3, gamma Subunit * MeSH
• Avian Proteins * MeSH

Birds represent important hosts for numerous viruses, including zoonotic viruses and pathogens with the potential to cause major economic losses to the poultry industry. Viral replication and transmission can be inhibited or blocked by the action of antiviral restriction factors (RFs) encoded by the host. One well-characterized RF is tetherin, a protein that directly blocks the release of newly formed viral particles from infected cells. Here, we describe the evolutionary loss of a functional tetherin gene in two galliform birds, turkey (Meleagris gallopavo) and Mikado pheasant (Syrmaticus mikado). Moreover, we demonstrate that the structurally related protein TMCC(aT) exerts antiviral activity in several birds, albeit by a mechanism different from that of tetherin. The evolutionary scenario described here represents the first documented loss-of-tetherin cases in vertebrates.

• Keywords
• gene loss, restriction factors, retroviruses, tetherin, turkey,
• MeSH
• Bone Marrow Stromal Antigen 2 genetics   MeSH
• Biological Evolution MeSH
• Antigens, CD genetics   metabolism   MeSH
• Galliformes * genetics   MeSH
• GPI-Linked Proteins * genetics   metabolism   MeSH
• Evolution, Molecular MeSH
• Avian Proteins genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Bone Marrow Stromal Antigen 2 MeSH
• Antigens, CD MeSH
• GPI-Linked Proteins * MeSH
• Avian Proteins MeSH

The Czech Republic, a part of the former Czechoslovakia, has been at the forefront of several research directions in virology, genetics and physiology [...].

• MeSH
• Virology * MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Editorial MeSH
• Geographicals
• Czech Republic MeSH