Enterovirus 71 leads to abnormal mitochondrial dynamics in human neuroblastoma SK-N-SH cells

• DOI: 10.1016/j.virusres.2023.199267
• Publication Date: 2023-11-15T21:22:38Z
• Authors: Wanling Zhang; Haiyan Yang; Zhengyun Liu; Shengyu Wang; Tianyang Chen; Hong Song; Yunbin Xu; Fajin Li; Guo Luo; Huan Wang
• Keywords: Nervous system; Infectious and parasitic diseases; RC109-216; Microbiology; Mitochondrial Dynamics; QR1-502; Article; 3. Good health; Enterovirus A, Human; Neuroblastoma; Mitochondrial dynamics; Enterovirus Infections; Humans; Enterovirus 71; Hand, Foot and Mouth Disease; Melatonin; Enterovirus

EV71, a significant pathogen causing hand-foot-mouth disease, is associated with severe neurological complications such as brain stem encephalitis, aseptic meningitis, and acute flaccid paralysis. While the role of mitochondrial dynamics in regulating the replication of numerous viruses is recognized, its specific involvement in EV71 remains unclear. This study aimed to elucidate the role of mitochondrial dynamics in human neuroblastoma SK-N-SH cells during EV71 infection. Utilizing laser confocal microscopy and transmission electron microscopy, we observed that EV71 infection induced mitochondrial elongation and damage to cristae structures, concurrently accelerating mitochondrial movement. Furthermore, we identified the reduction in the expression of dynamin-related protein 1 (Drp1) and optic atrophy protein 1 (Opa1) and the increased expression of Mitofusion 2 (Mfn2) upon EV71 infection. Notably, EV71 directly stimulated the generation of mitochondrial reactive oxygen species (ROS), leading to a decline in mitochondrial membrane potential and ATP levels. Remarkably, the application of melatonin, a potent mitochondrial protector, inhibited EV71 replication by restoring Drp1 expression. These findings collectively indicate that EV71 induces alterations in mitochondrial morphology and dynamics within SK-N-SH cells, potentially impairing mitochondrial function and contributing to nervous system dysfunction. The restoration of proper mitochondrial dynamics may hold promise as a prospective approach to counteract EV71 infection.