Why the study?
Molecular mechanisms underlying the neurovirulence and neuromuscular effects of Enterovirus A71 and D68 in severe neurological complications remain poorly understood.
Population
Human induced pluripotent stem cell-derived neuromuscular organoids
Comparison
EV-A71 infection vs EV-D68 infection
Design
In vitro experimental study
Key result
Infection of human neuromuscular organoids with EV-A71 and EV-D68 resulted in downregulation of neuronal and muscular gene networks, SNAP25 cleavage, and increased cleaved caspase-3 levels.
Authors
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This manuscript investigates the susceptibility of neuromuscular organoids (NMOs) derived from induced pluripotent stem cells to infection by enterovirus A71 (EV-A71) and enterovirus D68 (EV-D68). The authors conclude that both viruses infect neuronal populations within NMOs. However, the data presented do not convincingly support this claim.”
“The authors have generated neuromuscular organoids (NMOs) from human stem cells as a model for human infection of enteroviruses with known neurologic pathology using a strain of enterovirus A71 (EV-A71) from a genotype associated with neurologic disease and the prototype enterovirus D68 (EV-D68) which was not associated with neurologic disease. Nevertheless, both viruses did infect the NMOs producing changes in transcription of the host cells and detectable production of viral RNA and virus. Earlier work by Hixon et al (Reference 22) had demonstrated that the Fermon strain of EV-D68 would replicate in human motor neurons, demonstrating that there was a likelihood of infection of the NMOs with this strain despite the differences of the prototype from the contemporary EV-D68 strains associated with outbreaks of acute flaccid myelitis (AFM).”
“Schotting et al. clearly demonstrated the impact of non-polio enteroviruses on neuromuscular impairment using neuromuscular organoids.”
NMOs model EV neurovirulence in human tissue; leaves open clinical translation for AFM.
Human neuromuscular organoids serve as a robust platform to model enterovirus-induced acute flaccid myelitis, revealing distinct virus-specific transcriptomic and protein-level pathogenic effects.
Schotting et al. (2026) studied Enterovirus A71 and D68 infection. Enterovirus A71 (EV-A71) and enterovirus D68 (EV-D68) infection was evaluated on Cellular tropism and pathogenic effects. Infection of human neuromuscular organoids with EV-A71 and EV-D68 resulted in downregulation of neuronal and muscular gene networks, SNAP25 cleavage, and increased cleaved caspase-3 levels.