Metabolic reprogramming by Zika virus provokes inflammation in human placenta
Metabolic reprogramming by Zika virus provokes inflammation in human placenta
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DOI：
10.1038/s41467-020-16754-z
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发表时间：
2020-06-11
影响因子：
16.6
通讯作者：
Jabrane-Ferrat, Nabila
中科院分区：
文献类型：
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作者：
Chen, Qian;Gouilly, Jordi;Jabrane-Ferrat, Nabila
最近寨卡病毒（ZIKV）的爆发与妊娠早期发生母体感染时的出生缺陷和妊娠损失有关，但导致胎盘功能不全和随后ZIKV介导的发病机制仍不清楚。在这里，我们使用大规模代谢组学显示，ZIKV感染通过损害脂肪生成途径来重新编程胎盘脂质组。ZIKV诱导的代谢改变为脂滴生物发生和细胞内膜重排提供了构建模块，以支持病毒复制。此外，通过ZIKV的脂质体重编程被线粒体功能障碍和炎性免疫失衡所阻碍，这有助于胎盘损伤。此外，我们证明了市售抑制剂在限制ZIKV感染方面的功效，为通过靶向代谢途径阻断先天性感染提供了概念验证。总的来说，我们的研究提供了关于ZIKV如何靶向可能导致胎盘功能障碍和屏障功能丧失的脂质代谢的重要枢纽的机制见解。孕妇感染寨卡病毒（ZIKV）与妊娠丢失和出生缺陷有关，但病因学的分子见解很少。在这里，作者表明ZIKV重新编程宿主脂质组以促进病毒复制，诱导线粒体功能障碍并引起免疫失衡，从而确定ZIKV治疗的潜在靶标。
The recent outbreak of Zika virus (ZIKV) was associated with birth defects and pregnancy loss when maternal infection occurs in early pregnancy, but specific mechanisms driving placental insufficiency and subsequent ZIKV-mediated pathogenesis remain unclear. Here we show, using large scale metabolomics, that ZIKV infection reprograms placental lipidome by impairing the lipogenesis pathways. ZIKV-induced metabolic alterations provide building blocks for lipid droplet biogenesis and intracellular membrane rearrangements to support viral replication. Furthermore, lipidome reprogramming by ZIKV is paralleled by the mitochondrial dysfunction and inflammatory immune imbalance, which contribute to placental damage. In addition, we demonstrate the efficacy of a commercially available inhibitor in limiting ZIKV infection, provides a proof-of-concept for blocking congenital infection by targeting metabolic pathways. Collectively, our study provides mechanistic insights on how ZIKV targets essential hubs of the lipid metabolism that may lead to placental dysfunction and loss of barrier function. Zika virus (ZIKV) infection of pregnant women is associated with pregnancy loss and birth defects, but molecular insights for the aetiology are scarce. Here the authors show that ZIKV reprograms the host lipidome to facilitate viral replication, induce mitochondria dysfunction, and cause immune imbalance, thereby identifying a potential target for ZIKV therapy.