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While the avian orthoreovirus (ARV) \u03c3A 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\u2010I) but also markedly suppresses IFN\u2010mediated signal transduction. Further investigations revealed that the NDRV \u03c3A 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 \u03c3A protein regulates the JAK\u2010STAT signaling pathway. 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