Type I and type III interferon receptor knockout chickens: Novel models for unraveling interferon dynamics in influenza infection
Abstract The rapid cross-species transmission of highly pathogenic avian influenza presents a significant zoonotic threat. Elucidating the avian interferon (IFN) system, the primary antiviral defense in chickens, is critical for controlling the virus at its source and preventing its spillover into humans and other species. We engineered type I (IFN-α/β) and type III (IFN-λ) IFN receptor knockout chickens to dissect the role of IFNs in viral infections. Results revealed that type I IFN predominantly modulates innate immune cell populations, T cell subsets, and their contribution to antibody production following immunization under physiological conditions. In ovo and in vivo challenge experiments utilizing diverse influenza A virus strains demonstrated strain-specific roles of both IFN-α/β and IFN-λ in orchestrating viral pathogenesis, immunological responses, and tissue-tropism effects. Notably, type I IFN was particularly crucial in the initial defense mechanisms against H3N1 avian influenza A virus infection. These novel models offer unprecedented insights into avian IFN biology within the context of avian influenza, which is essential for developing more effective strategies to prevent and control this public health challenge.
Authors
- Rudolf Preisinger (ORCID: https://orcid.org/0000-0002-4873-0462)
- Romina Klinger
- Adrian Reich (ORCID: https://orcid.org/0000-0002-1680-8659)
- Hanna‐Kaisa Vikkula (ORCID: https://orcid.org/0009-0000-3208-1886)
- Simon Früh (ORCID: https://orcid.org/0000-0001-6804-5385)
- Christian Zenner (ORCID: https://orcid.org/0000-0003-4035-8456)
- Theresa von Heyl (ORCID: https://orcid.org/0000-0001-9936-5752)
- Milena Brunner
- Hicham Sid (ORCID: https://orcid.org/0000-0002-5608-8166)
- Lindsay Avolio (ORCID: https://orcid.org/0000-0002-5484-567X)
- Benjamin Schusser (ORCID: https://orcid.org/0000-0002-9990-1890)
- Silke Rautenschlein (ORCID: https://orcid.org/0000-0002-8177-3755)
- T.V.L. Berghof (ORCID: https://orcid.org/0000-0003-4879-6784)
- Mohanned Naif Alhussien (ORCID: https://orcid.org/0000-0002-3833-9953)
- Benjamin Schade
- Sabrina Schleibinger (ORCID: https://orcid.org/0009-0002-1264-4113)
- Bassel A Abukhadra
- Rashi Negi (ORCID: https://orcid.org/0009-0006-4918-3647)
Institutions
- Animal and Plant Health Inspection Service (US)
- University of Veterinary Medicine Hannover, Foundation (DE)
- BMW Group (Germany) (DE)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- Technical University of Munich (DE)
- Freie Universität Berlin (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Published
- 2025-09-10
- DOI
- https://doi.org/10.7554/elife.107855.1
- Citations
- 1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.35