The expression of IFN-ß 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 (3Dpoly) 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 3Dpoly 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 3Dpoly of EV-D68 can interact with PGAM5 and promote mitofusin 2 protein upregulation, and subsequently, 3Dpoly impairs IFN-ß expression by impacting the activation of the RIG-I receptor signaling pathway. Our findings suggest that during EV-D68 replication, the 3Dpoly, via its interaction with PGAM5, can affect the mitochondrial dynamics and suppress the expression of IFN-ß by impacting the RIG-I-like receptor signal pathway.

Single B cells reveal the antibody responses of rhesus macaques immunized with an inactivated enterovirus D68 vaccine.

Enterovirus D68 (EV-D68) infection may cause severe respiratory system manifestations in pediatric populations. Because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of EV-D68-specific vaccines and antibodies has become increasingly important. In this study, we prepared an experimental EV-D68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated EV-D68 vaccine exhibited potent neutralizing activity against EV-D68 virus in vitro. Subsequently, the antibody-mediated immune response of B cells elicited by the inactivated vaccine was evaluated in a rhesus monkey model. The binding activity, in vitro neutralization activity, and sequence properties of 28 paired antibodies from the rhesus macaques' EV-D68-specific single memory B cells were analyzed, and the EV-D68 VP1-specific antibody group was found to be the main constituent in vivo. Intriguingly, we also found a synergistic effect among the E15, E18 and E20 monoclonal antibodies from the rhesus macaques. Furthermore, we demonstrated the protective efficacy of maternal antibodies in suckling C57BL/6 mice. This study provides valuable information for the future development of EV-D68 vaccines.