期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 38, 页码 23869-23878出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2007773117
关键词
Zika virus; microcephaly; neurogenesis; pyroptosis; caspase-1
资金
- National Mega Project on Major Infectious Disease Prevention [2017ZX10103011]
- National Natural Science Foundation of China [81971146, 81870960, 81571992]
- Guangdong Basic and Applied Basic Research Foundation [2019A1515010937]
- Guangdong Marine Economy Promotion Projects Fund [GDOE [2019] A21]
- Guangdong Natural Science Funds for Distinguished Young Scholars [2014A030306023]
- Young Talent of Science and Technology Project of the Guangdong Te Zhi Program [2015TQ01R281]
Mounting evidence has associated Zika virus (ZIKV) infection with congenital malformations, including microcephaly, which raises global alarm. Nonetheless, mechanisms by which ZIKV disrupts neurogenesis and causes microcephaly are far from being understood. In this study, we discovered direct effects of ZIKV on neural progenitor cell development by inducing caspase-1- and gasdermin D (GSDMD)-mediated pyroptotic cell death, linking ZIKV infection with the development of microcephaly. Importantly, caspase-1 depletion or its inhibitor VX-765 treatment reduced ZIKV-induced inflammatory responses and pyroptosis, and substantially attenuated neuropathology and brain atrophy in vivo. Collectively, our data identify caspase-1- and GSDMD-mediated pyroptosis in neural progenitor cells as a previously unrecognized mechanism for ZIKV-related pathological effects during neural development, and also provide treatment options for ZIKV-associated diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据