Work

Enterovirus A71 exploits peripheral circulating extracellular vesicles to facilitate blood-brain barrier permeability

Year: 2026

Type: article

Abstract: Enterovirus A71 infection can cause hand, foot, and mouth disease to occasionally develop the severe neurological complications, but how peripheral Enterovirus A71 infection affects the blood-brain barrier remains incompletely understood. Here, we show that Enterovirus A71 infection of peripheral susceptible cells increases the release of extracellular vesicles and promotes the enrichment of microRNA-30 and microRNA-34 within these vesicles. The extracellular vesicle-associated microRNAs suppress Notch1 signaling in human brain microvascular endothelial cells, impair endothelial junctional integrity, and increase blood-brain barrier permeability. Activation of Notch1 signaling restores barrier integrity and reduces viral neuroinvasion in neonatal mice. Clinically, serum extracellular vesicle-associated microRNA-30 and microRNA-34 are elevated in patients with severe Enterovirus A71-associated hand, foot, and mouth disease. Together, our findings identify circulating extracellular vesicles as mediators linking peripheral Enterovirus A71 infection to blood-brain barrier dysfunction and suggest that the microRNA-30/34–Notch1 axis contributes to neurological disease progression during severe Enterovirus A71 infection. EV-A71 can cause severe neurological disease, but how peripheral infection disrupts the blood-brain barrier is unclear. Here, the authors show that circulating EVs carrying miRNA-30/34 suppress Notch1 signaling and increase BBB permeability in HBMECs.

Source: Nature Communications

DOI: 10.1038/s41467-026-79119-y