上睑下垂
寨卡病毒
胎儿
不利影响
生物
怀孕
胎盘
医学
免疫学
病毒
程序性细胞死亡
细胞凋亡
药理学
遗传学
作者
Zikai Zhao,Qi Li,Usama Ashraf,Mengjie Yang,Wenjing Zhu,Jun Gu,Zheng Chen,Changqin Gu,Youhui Si,Shengbo Cao,Jing Ye
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2022-08-16
卷期号:11
被引量:12
摘要
Zika virus (ZIKV) can be transmitted from mother to fetus during pregnancy, causing adverse fetal outcomes. Several studies have indicated that ZIKV can damage the fetal brain directly; however, whether the ZIKV-induced maternal placental injury contributes to adverse fetal outcomes is sparsely defined. Here, we demonstrated that ZIKV causes the pyroptosis of placental cells by activating the executor gasdermin E (GSDME) in vitro and in vivo. Mechanistically, TNF-α release is induced upon the recognition of viral genomic RNA by RIG-I, followed by activation of caspase-8 and caspase-3 to ultimately escalate the GSDME cleavage. Further analyses revealed that the ablation of GSDME or treatment with TNF-α receptor antagonist in ZIKV-infected pregnant mice attenuates placental pyroptosis, which consequently confers protection against adverse fetal outcomes. In conclusion, our study unveils a novel mechanism of ZIKV-induced adverse fetal outcomes via causing placental cell pyroptosis, which provides new clues for developing therapies for ZIKV-associated diseases.
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