Porcine haemagglutinating encephalomyelitis virus (PHEV) is a member of coronavirus that causes acute infectious disease and high mortality in piglets. The transcription factor IRF3 is a central regulator of type I interferon (IFN) innate immune signalling. Here, we report that PHEV infection of RAW264.7 cells results in strong suppression of IFN-β production in the early stage. A comparative analysis of the upstream effector of IFN-β transcription demonstrated that deactivation of IRF3, but not p65 or ATF-2 proteins, is uniquely attributed to failure of early IFN-β induction. Moreover, the RIG-I/MDA5/MAVS/TBK1-dependent protective response that regulates the IRF3 pathway is not disrupted by PHEV and works well underlying the deactivated IRF3-mediated IFN-β inhibition. After challenge with poly(I:C), a synthetic analogue of dsRNA used to stimulate IFN-β secretion in the TLR-controlled pathway, we show that PHEV and poly(I:C) regulate IFN-β-induction via two different pathways. Collectively, our findings reveal that deactivation of IRF3 is a specific mechanism that contributes to termination of type I IFN signalling during early infection with PHEV independent of the conserved RIG-I/MAVS/MDA5/TBK1-mediated innate immune response.

猪血凝性脑脊髓炎病毒（PHEV）是冠状病毒的成员，可引起仔猪急性传染病和高死亡率。转录因子IRF3是I型干扰素（IFN）先天免疫信号的中央调节器。在这里，我们报道RAW264.7细胞的PHEV感染会在早期强烈抑制IFN-β的产生。对IFN-β转录上游效应子的比较分析表明，IRF3的失活（而不是p65或ATF-2蛋白质）的失活是唯一归因于早期IFN-β诱导的失败。此外，调节IRF3途径的RIG-I / MDA5 / MAVS / TBK1依赖性保护反应不受PHEV干扰，并且在失活的IRF3介导的IFN-β抑制作用下表现良好。用poly（I：C）挑战后，dsRNA的合成类似物，用于刺激TLR控制途径中的IFN-β分泌，我们显示PHEV和聚（I：C）通过两种不同的途径调节IFN-β的诱导。总的来说，我们的发现表明，IRF3的失活是一种特殊的机制，可导致PHEV早期感染期间I型IFN信号终止，而独立于保守的RIG-I / MAVS / MDA5 / TBK1介导的先天免疫应答。