Enterovirus-A71 (EV-A71), known for causing Hand, Foot, and Mouth Disease, has been associated with severe neurological complications. A research team from the Institute of Molecular and Cell Biology (IMCB) has made significant progress in understanding how EV-A71 affects human motor neurons. The study, led by Dr. Shi-Yan Ng, in collaboration with Dr. Jonathan Loh’s team at IMCB, revealed that EV-A71 preferentially infects motor neurons, leading to cell death through a process called ferroptosis—a form of iron-dependent cell death. This discovery was made using a human motor neuron model derived from pluripotent stem cells.

The team found that EV-A71 infection results in an increase in intracellular iron levels and lipid peroxidation, which triggers ferroptosis. Importantly, the researchers showed that inhibiting ferroptosis using Deferoxamine (DFO), an iron chelator, could significantly improve the survival of infected neurons and restore mitochondrial function. These findings offer new insights into the neuropathogenesis of EV-A71 and suggest potential therapeutic strategies to mitigate its effects on the nervous system.

“Hand, Foot and Mouth Disease is usually mild, but in some children, severe neurological complications such as paralysis occurs. Our current study suggests that once the EV-71 virus breaches the blood-brain barrier, it preferentially infects the motor neurons, which can result in muscle weakness and paralysis,” said Dr. Ng. The study is a major step forward in understanding and potentially treating the neurological impact of EV-A71 infections.

This groundbreaking research has been published in Emerging Microbes & Infections.

Read more about the study here
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2382235