The Zika Virus Capsid Disrupts Corticogenesis by Suppressing Dicer Activity and miRNA Biogenesis
Research output: Contribution to journal › Journal article › Research › peer-review
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.
Original language | English |
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Journal | Cell Stem Cell |
Volume | 27 |
Issue number | 4 |
Pages (from-to) | 618-632.e9 |
ISSN | 1934-5909 |
DOIs | |
Publication status | Published - 1 Oct 2020 |
Bibliographical note
Publisher Copyright:
© 2020 Elsevier Inc.
- capsid, Dicer, microcephaly, miRNA, Zika virus
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541724/pdf/nihms-1619401.pdf
Accepted author manuscript
ID: 269517672