Zika virus causes placental pyroptosis and associated adverse fetal outcomes by activating GSDME
Zikai Zhao,
Qi Li,
Usama Ashraf,
Mengjie Yang,
Wenjing Zhu,
Jun Gu,
Zheng Chen,
Changqin Gu,
Youhui Si,
Shengbo Cao,
Jing Ye
Affiliations
Zikai Zhao
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Qi Li
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Usama Ashraf
Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Mengjie Yang
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Wenjing Zhu
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Jun Gu
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Zheng Chen
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Changqin Gu
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Youhui Si
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
Shengbo Cao
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China
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.
