Enterovirus D68 (EV-D68) belongs to the Picornaviridae family and can lead to severe clinical manifestations in the respiratory system. The 3D-polymerase (3D^poly) is an important nonstructural protein during EV-D68 replication, but few studies have addressed its interaction with the host antiviral response during EV-D68 infection. Here, we used human bronchial epithelial cells to investigate the impact of the 3D^poly on the mitochondrial dynamics and innate immune response. The results showed that the number and morphology of the mitochondria in 16HBE cells was affected during the early stage of infection, and these effects included the cellular apoptosis. Moreover, we found that the 3D^poly of EV-D68 can interact with PGAM5 and promote mitofusin 2 protein upregulation, and subsequently, 3D^poly impairs IFN-β expression by impacting the activation of the RIG-I receptor signaling pathway. Our findings suggest that during EV-D68 replication, the 3D^poly, via its interaction with PGAM5, can affect the mitochondrial dynamics and suppress the expression of IFN-β by impacting the RIG-I-like receptor signal pathway.

肠道病毒 D68 (EV-D68) 属于小核糖核酸病毒科，可导致呼吸系统出现严重的临床表现。3D-聚合酶 (3D ^poly ) 是 EV-D68 复制过程中的一种重要的非结构蛋白，但很少有研究涉及它在 EV-D68 感染过程中与宿主抗病毒反应的相互作用。在这里，我们使用人支气管上皮细胞来研究 3D^聚对线粒体动力学和先天免疫反应的影响。结果表明，16HBE细胞中线粒体的数量和形态在感染早期受到影响，这些影响包括细胞凋亡。此外，我们发现 3D^多边形EV-D68 可以与 PGAM5 相互作用并促进 mitofusin 2 蛋白上调，随后，3D ^poly通过影响 RIG-I 受体信号通路的激活来损害 IFN-β 表达。我们的研究结果表明，在 EV-D68 复制过程中，3D ^poly通过其与 PGAM5 的相互作用，可以影响线粒体动力学并通过影响 RIG-I 样受体信号通路来抑制 IFN-β 的表达。