Enterovirus A71 (EVA71) is a human enterovirus belonging to the Picornaviridae family and mostly causes hand-foot-and-mouth disease in infants. Viperin is an important interferon-stimulated gene with a broad antiviral activity against various viruses. However, the effect of viperin on human enteroviruses and the interaction mechanism between EVA71 and viperin remains elusive. Here, we confirmed the EVA71-induced expression of viperin in a mouse model and cell lines and showed that viperin upregulation by EVA71 infection occurred on both the mRNA and protein level. Viperin knockdown and overexpression in EVA71-infected cells indicated that this protein can markedly inhibit EVA71 infection. Interestingly, immunofluorescent confocal microscopy and co-immunoprecipitation assays indicated that viperin interacts and colocalizes with the EVA71 protein 2C in the endoplasmic reticulum. Furthermore, amino acids 50–60 in the N-terminal domain of viperin were the key residues responsible for viperin interaction with 2C. More importantly, the N-terminal domain of viperin was found responsible for inhibiting EVA71 replication. Our findings can potentially aid future research on the prevention and treatment of nervous system damage caused by EVA71 and may provide a potential target for antiviral therapy.

Enterovirus 71 (EV71) is the major causative pathogen of human hand, foot, and mouth disease (hHFMD) and has evolved to use various cellular receptors for infection. However, the relationship between receptor preference and EV71 virulence has not been fully revealed. By using reverse genetics, we identified that a single E98K mutation in VP1 is responsible for rapid viral replication in vitro. The E98K mutation enhanced binding of EV71-GZCII to cells in a heparan sulfate (HS)-dependent manner, and it attenuated the virulence of EV71-GZCII in BALB/c mice, indicating that the HS-binding property is negatively associated with viral virulence. HS is widely expressed in vascular endothelial cells in different mouse tissues, and weak colocalization of HS with scavenger receptor B2 (SCARB2) was detected. The cGZCII-98K virus bound more efficiently to mouse tissue homogenates, and the cGZCII-98K virus titers in mouse tissues and blood were much lower than the cGZCII virus titers. Together, these findings suggest that the enhanced adsorption of the cGZCII-98K virus, which likely occurs through HS, is unable to support the efficient replication of EV71 in vivo. Our study confirmed the role of HS-binding sites in EV71 infection and highlighted the importance of the HS receptor in EV71 pathogenesis.

Background: This study aimed to investigate the epidemiology and clinical characteristics of accidental corrosive agent ingestion in children and to identify factors associated with the severity of acute corrosive esophageal injury. Methods: We retrospectively analyzed demographic and clinical data of 138 children who accidentally ingested corrosive agents in a single center from July 2014 to October 2024. The severity of esophageal injury was assessed using the Zargar grading system (Grade 0-IV) during initial endoscopy. Univariate analysis and multivariate logistic regression were used to identify factors associated with acute esophageal injury. Results: The median age of the 138 children was 2.08 years (interquartile range: 1.54–3.27). Children aged ≤5 years accounted for 87.68% (121/138), with a male-to-female ratio of 2:1. Alkaline agents accounted for 75.36% (104/138), with pipe cleaners being the most common source (28.99%). Gastrointestinal symptoms were the most frequent presentation (42.03%), followed by oral symptoms (29.71%), while 28.26% were asymptomatic. The median hospital stay was 2 days. Initial endoscopy showed normal mucosa (Grade 0) in 98 cases (71.01%) and abnormal findings (Grade I–IIIb) in 40 cases (28.99%). Proton pump inhibitors were used in 127 cases (92.03%), and corticosteroids in 48 cases (34.78%). Univariate analysis revealed significant correlations between abnormal Zargar grade and both age and time from ingestion to hospital presentation (both P < 0.05). Multivariate logistic regression further identified that age ≤5 years (odds ratio = 0.30, 95% confidence interval: 0.10–0.86, P = 0.025) and time to presentation ≤6 hours (odds ratio = 0.43, 95% confidence interval: 0.19–0.96, P = 0.038) were independent protective factors against abnormal endoscopic findings. Among the 17 patients who completed follow-up (12.32%), 9 (52.94%) developed dysphagia and 8 (47.06%) developed esophageal strictures; however, the low follow-up rate and selection bias limit the generalizability of these findings. Conclusion: Age >5 years and time from ingestion to hospital presentation >6 hours are associated with an increased risk of acute esophageal injury in children following accidental corrosive ingestion (odds ratio = 3.33 and 2.33, respectively). Prompt medical evaluation and endoscopic assessment are recommended for children with suspected ingestion.