tetano
Editor, Senior Moderator
Elife
. 2026 Jun 26:14:RP107855.
doi: 10.7554/eLife.107855.
Deciphering interferon functions in avian influenza using receptor knockout models in the natural host
Mohanned Naif Alhussien[SUP] 1 [/SUP], Hanna Kaisa Vikkula[SUP] 1 [/SUP], Romina Klinger[SUP] 1 [/SUP], Christian Zenner[SUP] 1 [/SUP], Simon P Früh[SUP] 2 3 [/SUP], Rashi Negi[SUP] 1 [/SUP], Theresa von Heyl[SUP] 1 [/SUP], Sabrina Schleibinger[SUP] 1 [/SUP], Milena Brunner[SUP] 1 [/SUP], Tom V L Berghof[SUP] 1 [/SUP], Leora Avolio[SUP] 1 [/SUP], Arne Reich[SUP] 1 [/SUP], Benjamin Schade[SUP] 4 [/SUP], Bassel Aboukhadra[SUP] 5 [/SUP], Silke Rautenschlein[SUP] 5 [/SUP], Rudolf Preisinger[SUP] 6 [/SUP], Hicham Sid[SUP] 1 [/SUP], Benjamin Schusser[SUP] 1 7 [/SUP]
Affiliations
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.
Keywords: CRISPR/Cas9; avian influenza; chicken; genetic modification; immunology; inflammation; interferons.
. 2026 Jun 26:14:RP107855.
doi: 10.7554/eLife.107855.
Deciphering interferon functions in avian influenza using receptor knockout models in the natural host
Mohanned Naif Alhussien[SUP] 1 [/SUP], Hanna Kaisa Vikkula[SUP] 1 [/SUP], Romina Klinger[SUP] 1 [/SUP], Christian Zenner[SUP] 1 [/SUP], Simon P Früh[SUP] 2 3 [/SUP], Rashi Negi[SUP] 1 [/SUP], Theresa von Heyl[SUP] 1 [/SUP], Sabrina Schleibinger[SUP] 1 [/SUP], Milena Brunner[SUP] 1 [/SUP], Tom V L Berghof[SUP] 1 [/SUP], Leora Avolio[SUP] 1 [/SUP], Arne Reich[SUP] 1 [/SUP], Benjamin Schade[SUP] 4 [/SUP], Bassel Aboukhadra[SUP] 5 [/SUP], Silke Rautenschlein[SUP] 5 [/SUP], Rudolf Preisinger[SUP] 6 [/SUP], Hicham Sid[SUP] 1 [/SUP], Benjamin Schusser[SUP] 1 7 [/SUP]
Affiliations
- PMID: 42359495
- DOI: 10.7554/eLife.107855
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.
Keywords: CRISPR/Cas9; avian influenza; chicken; genetic modification; immunology; inflammation; interferons.