The expression of IFN-β is suppressed by the viral 3D polymerase via its impact on PGAM5 expression during enterovirus D68 infection.

Enterovirus D68 (EV-D68) belongs to the Picornaviridae family and can lead to severe clinical manifestations in the respiratory system. The 3D-polymerase (3D) 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 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 of EV-D68 can interact with PGAM5 and promote mitofusin 2 protein upregulation, and subsequently, 3D 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, 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.