Genetic reinstatement of RIG-I in chickens reveals insights into avian immune evolution and influenza interaction
Retinoic acid-inducible gene I (<i>RIG-I</i>) activates mitochondrial antiviral signaling proteins, initiating the antiviral response. <i>RIG-I</i> and <i>RNF135</i>, a ubiquitin ligase regulator, are missing in domestic chickens but conserved in mallard ducks. The chickens' <i>RIG-I</i> loss was long believed to be linked to increased avian influenza susceptibility. We reinstated both genes in chickens and examined their susceptibility to infection with an H7N1 avian influenza virus. Uninfected <i>RIG-I</i>-expressing chickens exhibited shifts in T and B cells. At the same time, the H7N1 infection led to severe disease, persistent weight loss, and increased viral replication. The simultaneous expression of <i>RIG-I</i> and <i>RNF135</i> potentiated the <i>RIG-</i>I activity and was associated with exacerbated inflammatory response and increased mortality without influencing virus replication. Additional animal infection experiments with two other avian influenza viruses validated these findings. They confirmed that the harmful effects triggered by <i>RIG-I</i> or <i>RIG-I</i>-<i>RNF135</i>-expression require a minimum degree of viral virulence. Our data indicate that the loss of <i>RIG-I</i> in chickens has likely evolved to counteract deleterious inflammation caused by viral infection and highlight an outcome of restoring evolutionary lost genes in birds.
Authors
- Romina Klinger
- Hanna‐Kaisa Vikkula (ORCID: https://orcid.org/0009-0000-3208-1886)
- Brigitte Böhm
- Rodrigo Guabiraba (ORCID: https://orcid.org/0000-0003-4005-1753)
- Daniel Elleder (ORCID: https://orcid.org/0000-0001-9041-5274)
- Theresa von Heyl (ORCID: https://orcid.org/0000-0001-9936-5752)
- Vanaïque Guillory
- Hicham Sid (ORCID: https://orcid.org/0000-0002-5608-8166)
- Lonneke Vervelde (ORCID: https://orcid.org/0000-0003-2241-1743)
- Benjamin Schusser (ORCID: https://orcid.org/0000-0002-9990-1890)
- Sascha Trapp (ORCID: https://orcid.org/0000-0002-2735-0217)
- Samantha Sives (ORCID: https://orcid.org/0000-0001-9234-1125)
- Mohanned Naif Alhussien (ORCID: https://orcid.org/0000-0002-3833-9953)
- Benjamin Schade
- Sabrina Schleibinger (ORCID: https://orcid.org/0009-0002-1264-4113)
- Leah Heymelot Nabel
- Ryan Scicluna
Institutions
- Université de Tours (FR)
- Roslin Institute (GB)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Department of Animal Health (VN)
- Biologie des oiseaux et aviculture (FR)
- Services déconcentrés d'appui à la recherche Val de Loire (FR)
- Institute of Molecular Genetics (RU)
- Czech Academy of Sciences, Institute of Molecular Genetics (CZ)
- Leibniz-Institute for Food Systems Biology at the Technical University of Munich (DE)
- Technical University of Munich (DE)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-10-08
- DOI
- https://doi.org/10.3389/fimmu.2025.1680791
- Citations
- 2
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 1.59