Role of autophagy in Zika virus infection and pathogenesis.

Role of autophagy in Zika virus infection and pathogenesis.
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DOI:
10.1016/j.virusres.2017.09.006
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发表时间:
2018-08-02
期刊:
影响因子:
5
通讯作者:
Best SM
Best SM
中科院分区:
医学3区
文献类型:
--
作者:
Chiramel AI;Best SM

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自噬是一种进化上保守的细胞途径,最终导致选定底物的溶酶体降解。自噬在病毒感染中可以发挥双重作用,具有促病毒或抗病毒功能,具体取决于病毒和病毒复制周期的阶段。最近的研究通过在体外和体内模型中证明 ZIKV 感染后自噬囊泡的积累,表明自噬在寨卡病毒 (ZIKV) 复制中的作用。在人类胎儿神经干细胞中,ZIKV 抑制 Akt-mTOR 信号传导以诱导自噬、增加病毒复制并阻碍神经发生。然而,自噬也有可能限制 ZIKV 复制,单独的研究表明自噬在母体-胎盘-胎儿界面上具有抗病毒作用,更具体地说,在受感染细胞中建立病毒复制的内质网上。有趣的是,ZIKV(和相关黄病毒)已经进化出了克服内质网自噬的特定机制,从而证明了这些自噬途径在病毒复制和宿主反应中的重要作用。这篇综述总结了自噬在 ZIKV 复制中的已知作用以及它们如何影响病毒组织趋向性和疾病。
Autophagy is an evolutionarily conserved cellular pathway that culminates in lysosomal degradation of selected substrates. Autophagy can serve dual roles in virus infection with either pro- or antiviral functions depending on the virus and the stage of the viral replication cycle. Recent studies have suggested a role for autophagy in Zika virus (ZIKV) replication by demonstrating the accumulation of autophagic vesicles following ZIKV infection in both in vitro and in vivo models. In human fetal neural stem cells, ZIKV inhibits Akt-mTOR signaling to induce autophagy, increase virus replication and impede neurogenesis. However, autophagy also has the potential to limit ZIKV replication, with separate studies demonstrating antiviral roles for autophagy at the maternal-placental-fetal interface, and more specifically, at the endoplasmic reticulum where virus replication is established in an infected cell. Interestingly, ZIKV (and related flaviviruses) has evolved specific mechanisms to overcome autophagy at the ER, thus demonstrating important roles for these autophagic pathways in virus replication and host response. This review summarizes the known roles of autophagy in ZIKV replication and how they might influence virus tissue tropism and disease.
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