Zika Virus Causes Placental Pyroptosis and Associated Adverse Fetal Outcomes by Activating GSDME

Overview

Journal Elife

Specialty Biology

Date 2022 Aug 16

PMID 35972780

Authors

Zikai Zhao

Qi Li

Usama Ashraf

Mengjie Yang

Wenjing Zhu

Jun Gu

Zheng Chen

Changqin Gu

Youhui Si

Shengbo Cao

Jing Ye

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Zika virus-induced fetal demise is driven by strain- and dose-specific RLR-driven activation of the interferon response in the decidua, placenta, and fetus in mice.

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