Fowl adenovirus serotype 4 ORF1B protein suppresses type I interferon production by inhibiting IRF7 nuclear translocation.

Fowl adenovirus serotype 4 (FAdV-4), the causative agent of hepatitis-hydropericardium syndrome (HHS), has been reported to counter the host innate immune response. However, the underlying mechanisms employed by FAdV-4 to block cellular antiviral defense remain unclear. With a functional screen, we identified three FAdV-4 proteins that antagonized beta interferon (IFN-β) production induced by poly (dA:dT) and cGAS/STING in chicken fibroblasts. Specifically, the FAdV-4 unique nonstructural protein ORF1B exhibited the strongest inhibitory effect by targeting interferon regulatory factor 7 (IRF7). Further data found that ORF1B interacted with IRF7 to inhibit its nuclear translocation. Ectopic expression of IRF7 blocked the replication of FAdV-4, with virus titers and viral protein synthesis greatly lower than those of the control group. Conversely, knockdown of IRF7 promoted FAdV-4 replication in vitro. These findings illustrate the potential mechanism that allows FAdV-4 to evade host antiviral immunity.