PHB1 and PHB2 positively regulate IFN-β production by targeting MAVS in ducks

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Mitochondrial prohibitin (PHB) complex subunits PHB1 and PHB2 regulate innate antiviral immunity.
• Ducks are natural reservoirs for RNA viruses, possessing unique antiviral mechanisms involving RIG-I.
• The specific roles of PHB1 and PHB2 in the duck RIG-I-MAVS-IFN-β pathway are not well understood.

Purpose of the Study:

• To characterize the structure and function of duck PHB1 and PHB2 (duPHB1/2).
• To investigate the involvement of duPHB1/2 in the RIG-I-MAVS-IFN-β signaling pathway and antiviral innate immunity in ducks.

Main Methods:

• Structural and functional domain characterization of duPHB1 and duPHB2.
• Gene expression analysis in various duck tissues post-NDV infection.
• Overexpression and siRNA-mediated knockdown experiments in duck embryonic fibroblasts (DEFs).
• MAVS depletion assays to confirm pathway dependence.

Main Results:

• duPHB1 and duPHB2 share conserved structural domains with orthologs and are widely expressed, with higher levels in immune organs and metabolically active tissues post-NDV infection.
• Overexpression of duPHB1/2 enhanced MAVS activation and IFN-β production, while knockdown suppressed these responses.
• duPHB1 and duPHB2 synergistically boosted MAVS-dependent IFN-β induction, which was abolished upon MAVS depletion.

Conclusions:

• duPHB1 and duPHB2 are key regulators of mitochondrial-mediated antiviral responses in ducks.
• These proteins play a critical role in the MAVS-dependent IFN-β production pathway, enhancing avian innate immunity.
• Findings provide insights into the unique antiviral mechanisms of ducks.