Avian interferon regulatory factor (IRF) family reunion: IRF3 and IRF9 found
Language English Country Great Britain, England Media electronic
Document type Journal Article
Grant support
GA23-07210S
Grantová Agentura České Republiky
GA23-07210S
Grantová Agentura České Republiky
GA23-07210S
Grantová Agentura České Republiky
GA23-07210S
Grantová Agentura České Republiky
FOR5130
Deutsche Forschungsgemeinschaft
FOR5130
Deutsche Forschungsgemeinschaft
PubMed
40597257
PubMed Central
PMC12220609
DOI
10.1186/s12915-025-02261-4
PII: 10.1186/s12915-025-02261-4
Knihovny.cz E-resources
- 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
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.
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