Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target.
Proc Natl Acad Sci U S A
; 117(38): 23869-23878, 2020 09 22.
Article
en En
| MEDLINE
| ID: mdl-32907937
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Encefalopatías
/
Células-Madre Neurales
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Piroptosis
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Virus Zika
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Infección por el Virus Zika
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2020
Tipo del documento:
Article
País de afiliación:
China