Exosomal MicroRNA-155 Inhibits Enterovirus A71 Infection by Targeting PICALM
Exosomal MicroRNA-155 Inhibits Enterovirus A71 Infection by Targeting PICALM
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外泌体 MicroRNA-155 通过靶向 PICALM 抑制肠道病毒 A71 感染
DOI：
10.7150/ijbs.36388
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发表时间：
2019-01-01
影响因子：
9.2
通讯作者：
Mao, Lingxiang
中科院分区：
文献类型：
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作者：
Wu, Jing;Gu, Jiaqi;Mao, Lingxiang
肠道病毒A71(EV-A71)可引起手足口病(HFMD)，与神经系统并发症有关。研究人员已经证明，含有宿主细胞microRNA(MiRNA)的外切体可以在病毒感染期间调节接受者的细胞反应。然而，目前尚不清楚外体miRNAs在EV-A71感染过程中如何调节这种反应。在本研究中，我们使用外体miRNA芯片显示，在EV-A71感染后，microRNA-155(miR-155)显著富含在外体中。此外，外体miR-155通过靶向受体细胞中的磷脂酰肌醇蛋白组装蛋白(PICALM)，有效地抑制了EV-A71的感染。重要的是，我们证实了外体miR-155在体内降低了EV-A71感染的严重程度。此外，EV-A71感染患者咽拭子中miR-155的水平高于健康人。综上所述，我们的发现提供了证据，表明外体miR-155通过抑制PICALM介导EV-A71感染，在宿主-病原体相互作用中发挥作用；这些结果为病毒感染的调控机制提供了见解。
Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease (HFMD) that is associated with neurological complications. Researchers have shown that exosomes containing host cellular microRNA (miRNA) can modulate the recipient's cellular response during viral infection. However, it is unclear how exosomal miRNAs regulate this response during EV-A71 infection. In this study, we used an exosomal miRNA chip to show that microRNA-155 (miR-155) was markedly enriched in exosomes after EV-A71 infection. Moreover, exosomal miR-155 efficaciously inhibited EV-A71 infection by targeting phosphatidylinositol clathrin assembly protein (PICALM) in recipient cells. Importantly, we confirmed that exosomal miR-155 reduced EV-A71 infection severity in vivo. Additionally, miR-155 levels in throat swabs from EV-A71-infected patients were higher than in those from healthy individuals. Collectively, our findings provide evidence that exosomal miR-155 plays a role in host-pathogen interactions by mediating EV-A71 infection via the repression of PICALM; these results provide insights into the regulatory mechanisms of viral infection.