Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan; Life Science Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Kanagawa, 259-1146, Japan.
Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan.
Biochem Biophys Res Commun. 2021 Jan 1;534:666-671. doi: 10.1016/j.bbrc.2020.11.023. Epub 2020 Nov 15.
The association of Zika virus (ZIKV) infection with a congenital malformation in fetuses, neurological, and other systemic complications in adults have brought significant global health emergency. ZIKV targets nerve cells in the brain and causes cell death, such as pyroptosis, leading to neuroinflammation. Here we described a novel mechanism of pyroptosis caused by ZIKV protease. We found that ZIKV protease directly cleaved the GSDMD into N-terminal fragment (1-249) leading to pyroptosis in a caspase-independent manner, suggesting a direct mechanism of ZIKV-induced cell death and subsequent inflammation. Our findings might shed new light to explore the pathogenesis of ZIKV infections where ZIKV protease might be a suitable target for the development of antiviral agents.
寨卡病毒（ZIKV）感染与胎儿先天性畸形、成人神经和其他系统并发症相关，已构成重大全球卫生紧急事件。ZIKV 靶向大脑中的神经细胞，并导致细胞死亡，如细胞焦亡，引发神经炎症。在此，我们描述了 ZIKV 蛋白酶引起细胞焦亡的一种新机制。我们发现，ZIKV 蛋白酶直接将 GSDMD 切割成 N 端片段（1-249），从而以胱天蛋白酶非依赖性方式引发细胞焦亡，提示了 ZIKV 诱导细胞死亡和随后炎症的直接机制。我们的研究结果可能为探索 ZIKV 感染的发病机制提供新的思路，ZIKV 蛋白酶可能是开发抗病毒药物的合适靶点。
