Deciphering interferon functions in avian influenza using receptor knockout models in the natural host

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Highly pathogenic avian influenza poses a zoonotic risk.
• The avian interferon (IFN) system is a critical antiviral defense in chickens.
• Understanding IFN roles is vital for controlling avian influenza and preventing human spillover.

Purpose of the Study:

• To dissect the roles of type I (IFN-α/β) and type III (IFN-λ) interferons in avian antiviral immunity.
• To investigate the impact of IFNs on immune cell modulation and antibody production.
• To elucidate the strain-specific functions of IFNs in avian influenza virus (AIV) pathogenesis and tissue tropism.

Main Methods:

• Engineered type I and type III IFN receptor knockout chickens.
• Conducted in ovo and in vivo challenge experiments with diverse influenza A virus strains.
• Analyzed immune cell populations, T cell subsets, and antibody production.

Main Results:

• Type I IFN primarily modulates innate immune cells, T cell subsets, and antibody production.
• Both IFN-α/β and IFN-λ exhibit strain-specific roles in viral pathogenesis, immune response, and tissue tropism.
• Type I IFN is particularly critical for early defense against H3N1 avian influenza A virus.

Conclusions:

• Novel IFN receptor knockout chicken models provide insights into avian IFN biology.
• These findings are essential for developing effective strategies against avian influenza.
• Understanding IFN pathways is crucial for controlling zoonotic threats from avian influenza.