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Series GSE137592 Query DataSets for GSE137592
Status Public on Aug 04, 2020
Title Virus-Host Interactome Reveals the Unique Blockage of Host RNAi Machinery by the Zika Virus Capsid
Organism Homo sapiens
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary The recent outbreaks of Zika virus (ZIKV) and its association with birth defects known as Congenital Zika Syndrome warrant investigation on the molecular processes related to its infection and pathogenesis. Among the flavivirus family, only ZIKV is linked to microcephaly as announced by World Health Organization, suggesting uniqueness of ZIKV infection compared to other members. By analyzing the ZIKV-host interactome, we found that the key microRNA (miRNA) processing enzyme Dicer was a leading target of ZIKV capsid protein in neural stem cells (NSCs), and its deficiency facilitated ZIKV infection. Mechanistically, ZIKV capsid can directly interact with Dicer and block its ribonuclease activity, dampening the production of host miRNAs that are essential for neurogenesis. Interestingly, this capsid-mediated immune evasion is specific to ZIKV because capsid proteins from other close flaviviruses, e.g., dengue, yellow fever and West Nile viruses, cannot bind to Dicer or inhibit its function. By molecular mapping, we defined a ZIKV capsid H41R mutant with loss of interaction to Dicer and no longer affecting its activity. More importantly, ZIKV H41R mutant exerted almost no impact on neurogenesis in vitro when expressed in NSCs compared to wild type capsid, and in utero infection of recombinant ZIKV-H41R mutant virus resulted in less inhibition on corticogenesis than wild-type ZIKV in mouse embryos. Interestingly, the epidemic ZIKV strain reinforces the capsid-Dicer interaction by two amino acid substitution compared to ancient Africa strain. Thus, our study demonstrated that capsid-dependent suppression of Dicer function is a unique determinant of ZIKV immune evasion and pathogenesis, which may unveil a new mechanism for ZIKV-mediated microcephaly.
Overall design miRNA-seq of neural stem cells (NSCs) infected with ZKIV or ZKIV H41R or without infection
Contributor(s) Zeng J, Dong S, Luo Z, Fu B, Li P, Xie X, Yang X, Chen Y, Wang X, Liu C, Liu Z, Wu J, Zhang J, Long G, Ding S, Li S, Zhao Z, Liang Q
Citation(s) 32763144
Submission date Sep 17, 2019
Last update date Nov 16, 2020
Contact name Zhifei Luo
Organization name University of Southern California
Street address 1450 Biggy Street, NRT 6514
City Los Angeles
State/province CA
ZIP/Postal code 90089-9601
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (9)
GSM4082154 Mock_1
GSM4082155 Mock_2
GSM4082156 Mock_3
BioProject PRJNA565978
SRA SRP222066

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Supplementary file Size Download File type/resource
GSE137592_raw_read_counts.txt.gz 509.6 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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