The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis
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The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis. / Zeng, Jianxiong; Dong, Shupeng; Luo, Zhifei; Xie, Xiaochun; Fu, Bishi; Li, Ping; Liu, Chengrong; Yang, Xing; Chen, Yujie; Wang, Xin; Liu, Zhenshan; Wu, Jing; Yan, Youzhen; Wang, Feng; Chen, Jian Fu; Zhang, Jian; Long, Gang; Goldman, Steven A.; Li, Shitao; Zhao, Zhen; Liang, Qiming.
In: Cell Stem Cell, Vol. 27, No. 4, 01.10.2020, p. 618-632.e9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis
AU - Zeng, Jianxiong
AU - Dong, Shupeng
AU - Luo, Zhifei
AU - Xie, Xiaochun
AU - Fu, Bishi
AU - Li, Ping
AU - Liu, Chengrong
AU - Yang, Xing
AU - Chen, Yujie
AU - Wang, Xin
AU - Liu, Zhenshan
AU - Wu, Jing
AU - Yan, Youzhen
AU - Wang, Feng
AU - Chen, Jian Fu
AU - Zhang, Jian
AU - Long, Gang
AU - Goldman, Steven A.
AU - Li, Shitao
AU - Zhao, Zhen
AU - Liang, Qiming
N1 - Publisher Copyright: © 2020 Elsevier Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.
AB - Zika virus (ZIKV) causes microcephaly and disrupts neurogenesis. Dicer-mediated miRNA biogenesis is required for embryonic brain development and has been suggested to be disrupted upon ZIKV infection. Here we mapped the ZIKV-host interactome in neural stem cells (NSCs) and found that Dicer is specifically targeted by the capsid from ZIKV, but not other flaviviruses, to facilitate ZIKV infection. We identified a capsid mutant (H41R) that loses this interaction and does not suppress Dicer activity. Consistently, ZIKV-H41R is less virulent and does not inhibit neurogenesis in vitro or corticogenesis in utero. Epidemic ZIKV strains contain capsid mutations that increase Dicer binding affinity and enhance pathogenicity. ZIKV-infected NSCs show global dampening of miRNA production, including key miRNAs linked to neurogenesis, which is not observed after ZIKV-H41R infection. Together these findings show that capsid-dependent suppression of Dicer is a major determinant of ZIKV immune evasion and pathogenesis and may underlie ZIKV-related microcephaly.
KW - capsid
KW - Dicer
KW - microcephaly
KW - miRNA
KW - Zika virus
U2 - 10.1016/j.stem.2020.07.012
DO - 10.1016/j.stem.2020.07.012
M3 - Journal article
C2 - 32763144
AN - SCOPUS:85089983757
VL - 27
SP - 618-632.e9
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 4
ER -
ID: 269517672