Novel Duck Orthoreovirus σA Protein Inhibits Interferon Signaling by Impeding STAT1/STAT2 Nuclear Translocation

Novel duck orthoreovirus (NDRV) infection induces severe splenic necrosis and immunosuppression in ducks, leading to substantial economic losses in the duck farming industry. While the avian orthoreovirus (ARV) σA protein is known to exhibit interferon (IFN) antagonistic activity, whether NDRV possesses a similar function and the underlying molecular mechanisms remain unclear. This study demonstrates that NDRV not only counteracts the antiviral clearance effect of type I IFN (IFN‐I) but also markedly suppresses IFN‐mediated signal transduction. Further investigations revealed that the NDRV σA protein specifically inhibits IFN signaling and its associated antiviral effects by blocking the nuclear translocation of STAT1/STAT2, thereby, facilitating innate immune escape. This discovery elucidates for the first time a novel mechanism by which the NDRV σA protein regulates the JAK‐STAT signaling pathway. These findings provide a theoretical foundation for the development of antiviral strategies targeting immune regulation.