biostudies-literatureChooi WHNational Research Foundation Singapore2382235https://www.ebi.ac.uk/biostudies/studies/S-EPMC11285248biostudies-literatureUnknown13(1)Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labilEmerging microbes & infectionsEnterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis.PMC11285248NRF-CRP21-2018-0004Chooi WHChu JJHWinantoGautam PAlonso SLoh YHLee CYNg SYZeng YLim ZQfalseEnterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis.Enterovirus A71 (EV-A71) causes Hand, Foot, and Mouth Disease and has been clinically associated with neurological complications. However, there is a lack of relevant models to elucidate the neuropathology of EV-A71 and its mechanism, as the current models mainly utilize animal models or immortalized cell lines. In this study, we established a human motor neuron model for EV-A71 infection. Single cell transcriptomics of a mixed neuronal population reveal higher viral RNA load in motor neurons, suggesting higher infectivity and replication of EV-A71 in motor neurons. The elevated RNA load in motor neurons correlates with the downregulation of ferritin-encoding genes. Subsequent analysis confirms that neurons infected with EV-A71 undergo ferroptosis, as evidenced by increased levels of labil2024-01-01T00:00:00Z2024 Dec2026-06-02T18:39:37.024Z2025-08-23T03:05:15.464ZS-EPMC112852483901765510.1080/22221751.2024.2382235