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| Status |
Public on Aug 16, 2019 |
| Title |
Effect of ZIKV on pre-implantation embryos |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
To determine the effect of Zika virus infection on pre-implantation embryonic development, we performed single blastocyst RNA-Seq on MOCK and ZIKV infected embryos. ZIKV infection results in an increased risk of spontaneous abortion and poor intrauterine growth although the mechanisms underlying fetal loss remain undetermined. Little is known about the impact of ZIKV infection during the earliest stages of pregnancy, or pre- and peri-implantation, because most current studies of ZIKV infection in pregnancy models focus on post-implantation stages. Here, we demonstrate that trophectoderm cells of pre-implantation human and mouse embryos can be efficiently infected with ZIKV, and that trophectoderm can propagate virus causing cell death of neural progenitors. These findings were corroborated by our demonstration that hESC-derived trophectoderm cells are infected by ZIKV in a dose dependent manner. RNAseq of single blastocysts revealed key transcriptional changes in cellular and physiologic functions upon ZIKV infection, including nervous system development and function, prior to commitment to the neural cell lineage. Finally, the pregnancy rate of mice infected pre-implantation was > 50% lower than females infected at E4.5. These results demonstrate that pre-implantation ZIKV infection of trophectoderm leads to miscarriage or spontaneous abortion. Moreover, pre- and peri-implantation ZIKV infects trophectoderm cells that propagate virus over time causing cell death in neural progenitors. Cumulatively, these data demonstrate that vertical pre- and peri-implantation ZIKV infection of trophectoderm impairs fetal development and causes neural progenitor cell death, elucidating a previously unappreciated association of pre- and peri-implantation ZIKV infection and microcephaly.
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| Overall design |
Single Blastocyst RNASeq of Mock (n=5 samples) and Zika (n=7 samples) infected mouse blastocysts
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| Contributor(s) |
Lacko LA, Tan L, Chen S |
| Citation(s) |
31519912 |
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| Submission date |
Jun 25, 2019 |
| Last update date |
Sep 23, 2019 |
| Contact name |
Shuibing Chen |
| E-mail(s) |
shuibing.chen@gmail.com
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| Phone |
2127465431
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| Organization name |
Weill Cornell Medical College
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| Department |
Surgery
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| Street address |
A 827B, 1300 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA550525 |
| SRA |
SRP211899 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE133254_Processed_gene_expression.xlsx |
4.7 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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