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| Status |
Public on Apr 15, 2019 |
| Title |
Zika virus infection induces RNAi-mediated antiviral immunity in human neural progenitors and brain organoids |
| Organisms |
Aedes aegypti; Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
The re-emergence of Zika virus (ZIKV) in the Western Hemisphere has resulted in global public health crisis since 2015. ZIKV
preferentially infects and targets human neural progenitor cells (hNPCs) and causes fetal microcephaly upon maternal infection.
hNPCs not only play critical roles during fetal brain development, but also persist in adult brain throughout life. Yet the mechanism
of innate antiviral immunity in hNPCs remains largely unknown. Here, we show that ZIKV infection triggers the abundant
production of virus-derived small interfering RNAs in hNPCs, but not in the more differentiated progenies or somatic cells. Ablation
of key RNAi machinery components significantly enhances ZIKV replication in hNPCs. Furthermore, enoxacin, a broad-spectrum
antibiotic that is known as an RNAi enhancer, exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells. Strikingly,
enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid
models that recapitulate human fetal brain development. Our findings highlight the physiological importance of RNAi-mediated
antiviral immunity during the early stage of human brain development, uncovering a novel strategy to combat human congenital
viral infections through enhancing RNAi.
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| Overall design |
Small RNA profile of virus-infected cells
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| Contributor(s) |
Xu Y, Qiu Y, Zhang B, Chen G, Chen Q, Wang M, Mo F, Xu J, Wu J, Zhang R, Cheng M, Zhang N, Lyu B, Zhu W, Wu M, Ye Q, Zhang D, Man J, Li X, Cui J, Xu Z, Hu B, Zhou X, Qin C |
| Citation(s) |
30814679 |
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| Submission date |
Jan 23, 2019 |
| Last update date |
Jul 15, 2019 |
| Contact name |
xi zhou |
| E-mail(s) |
zhouxi@wh.iov.cn
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| Organization name |
Wuhan University
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| Department |
State Key Laboratory of Virology, College of Life Sciences
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| Street address |
Luojia Hill
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| City |
Wuhan |
| State/province |
Hubei |
| ZIP/Postal code |
430072 |
| Country |
China |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL21020 |
Illumina HiSeq 2000 (Aedes aegypti) |
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| Samples (5)
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| Relations |
| BioProject |
PRJNA516662 |
| SRA |
SRP181655 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE125520_RAW.tar |
2.8 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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