Zika virus depletes neural stem cells and evades selective autophagy by suppressing the Fanconi anemia protein FANCC.

Abstract:

:Zika virus (ZIKV) is an emerging flavivirus, which when passed through vertical transmission from mother to developing fetus can lead to developmental abnormalities, including microcephaly. While there is mounting evidence that suggests a causal relationship between ZIKV infection and microcephaly, the mechanisms by which ZIKV induces these changes remain to be elucidated. Here, we demonstrate that ZIKV infection of neural stems cells, both in vitro and in vivo, induces macroautophagy to enhance viral replication. At the same time, ZIKV downregulates a number of essential selective autophagy genes, including the Fanconi anemia (FA) pathway genes. Bioinformatics analyses indicate that the transcription factor E2F4 promotes FANCC expression and is downregulated upon ZIKV infection. Gain and loss of function assays indicate that FANCC is essential for selective autophagy and acts as a negative regulator of ZIKV replication. Finally, we show that Fancc KO mice have increased ZIKV infection and autophagy protein levels in various brain regions. Taken together, ZIKV downregulates FANCC to modulate the host antiviral response and simultaneously attenuate neuronal growth.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Tiwari SK,Dang JW,Lin N,Qin Y,Wang S,Rana TM

doi

10.15252/embr.201949183

subject

Has Abstract

pub_date

2020-10-19 00:00:00

pages

e49183

eissn

1469-221X

issn

1469-3178

pub_type

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