Neural Progenitor Cell Pyroptosis Contributes to Zika Virus-induced Brain Atrophy and Represents a Therapeutic Target

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2020 Sep 10

PMID 32907937

Citations 39

Authors

Zhenjian He

Shu An

Jiahui Chen

Shuqing Zhang

Chahui Tan

Jianchen Yu

Hengming Ye

Yun Wu

Jie Yuan

Jueheng Wu

Xun Zhu

Mengfeng Li

Affiliations

Soon will be listed here.

Abstract

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.

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