Microvesicles carrying EV71 virions cross BBB through endocytic pathway to induce brain injury

作者：Xiaoyan Tian, Bingxin Liu, Linrun Li, Meng Yuan, Qiao You, Rui Zhang, Deyan Chen, Min Cheng, Nan Zheng, Miao He, Zhiwei Wu · 发表于：Cell Communication and Signaling · 年份：2025 · DOI：10.1186/s12964-025-02195-y · 被引用次数：10 · 研究领域：Extracellular vesicles in disease、Mosquito-borne diseases and control、Viral Infections and Vectors

Enterovirus 71 (EV71) is a major etiologic pathogen for hand-foot-and-mouth disease (HFMD) in young children. Severe cases of EV71 infection could lead to neurological complications and even death, while the mechanism inducing neurological complications remains poorly understood. In this study, we firstly proved that microvesicles (MVs) could carry EV71 virions and mediate a higher efficiency in infection. Utilizing an in vitro blood-brain barrier (BBB) model, we observed that MVs containing virions (MVsEV71) could cross the BBB with greater efficiency compared to EV71 alone. Through in vivo imaging, we confirmed the ability of MVs to cross the BBB. qPCR assays showed a higher copy number of EV71 in both blood and brain samples in the mice treated with MVsEV71 compared to those treated with free EV71. Also, our investigation unveiled that MVsEV71 infection of animals induced cerebral hemorrhage and more severe inflammatory infiltration in the brain compared to animals infected by EV71 in vivo. Furthermore, we found a reduction in the expression of junction proteins such as zonula occludens-1 (ZO-1) and occludin. Moreover, the uptake of MVs by brain cells was examined using chemical inhibitor to block the endocytic pathway. Our experiments elucidated that the internalization of MVs occurred via a non-clathrin-dependent mechanism and a portion of the internalized MVs proceeded to enter lysosomes. In addition, we identified damaged mitochondria as the "cargo" of MVs, which facil...