Pexophagy Triggered by Enterovirus 71 Modulates the Production of Pro-Inflammatory Cytokines Through Cholesterol Accumulation in Lysosomes

Mounting evidence indicates that pexophagy plays a pivotal role in various physiological and pathological processes. However, the crosstalk between pexophagy and enterovirus 71 (EV71) replication remains to be illustrated. The study aims to explore the molecular mechanisms and pathogenesis underlying the role of pexophagy in EV71 infection. In this study, our findings confirm and extend previous observations that autophagy facilitates EV71 replication. Next, we present strong novel evidence that EV71 replication can trigger excessive hydrogen peroxide in peroxisomes by mislocalization of peroxisomal catalase, leading to pexophagy. Moreover, our data indicate that dysfunctional peroxisomes elicit cholesterol accumulation in lysosomes, contributing to upregulated level of production of pro-inflammatory cytokines. Collectively, our study demonstrates that pexophagy may act as a new candidate player involved in the pathogenesis of EV71 infection via regulating oxidative stress status and inflammation, which provides a solid basis for the development of novel antivirus treatment.