Genome-wide CRISPR screen for Zika virus resistance in human neural cells.
Proc Natl Acad Sci U S A
; 116(19): 9527-9532, 2019 05 07.
Article
em En
| MEDLINE
| ID: mdl-31019072
ABSTRACT
Zika virus (ZIKV) is a neurotropic and neurovirulent arbovirus that has severe detrimental impact on the developing human fetal brain. To date, little is known about the factors required for ZIKV infection of human neural cells. We identified ZIKV host genes in human pluripotent stem cell (hPSC)-derived neural progenitors (NPs) using a genome-wide CRISPR-Cas9 knockout screen. Mutations of host factors involved in heparan sulfation, endocytosis, endoplasmic reticulum processing, Golgi function, and interferon activity conferred resistance to infection with the Uganda strain of ZIKV and a more recent North American isolate. Host genes essential for ZIKV replication identified in human NPs also provided a low level of protection against ZIKV in isogenic human astrocytes. Our findings provide insights into host-dependent mechanisms for ZIKV infection in the highly vulnerable human NP cells and identify molecular targets for potential therapeutic intervention.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Replicação Viral
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Células-Tronco Neurais
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Resistência à Doença
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Sistemas CRISPR-Cas
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Zika virus
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Infecção por Zika virus
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2019
Tipo de documento:
Article