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Status |
Public on May 18, 2020 |
Title |
Molecular Alterations of Extracellular Matrix in the Brain of Newborns with Congenital Zika Syndrome |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Zika virus (ZIKV) infection during pregnancy could cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments using animal models and in vitro systems significantly contributed to our understanding of the physiopathology of ZIKV infection. However, the molecular basis of CZS is not yet studied in humans. Here, we used a systems biology approach to integrate transcriptomic, proteomic and genomic data from post-mortem brains of neonates with CZS. We observed that collagen genes were greatly reduced in CZS brains at both the RNA and protein levels and that neonates with CZS have several polymorphisms in collagen genes associated with osteogenesis imperfect and arthrogryposis. These findings were validated using immunohistochemistry and collagen staining of ZIKV infected and non-infected samples. Additionally, it was found that cell adhesion genes that are essential for neurite outgrowth and axon guidance were up-regulated and thereby confirmed the neuronal migration defects observed. This work provided new insights into the underlying mechanisms of CZS and revealed host genes associated with CZS susceptibility.
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Overall design |
RNA-seq of post-mortem cortex samples from ZIKV infected infants with microcephaly
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Contributor(s) |
Aguiar RS, Pohl F, Morais GL, Nogueira FC, Carvalho JB, Guida L, Arge LW, Melo A, Moreira ME, Cunha DP, Gomes L, Portari EA, Velasquez E, Melani RD, Pezzuto P, de Castro FL, Geddes VE, Gerber AL, Azevedo GS, Schamber-Reis BL, Gonçalves AL, Azevedo IJ, Junior MY, Ho PL, Schanoski AS, Schuch V, Tanuri A, Chimelli L, Vasconcelos ZF, Domont GB, Vasconcelos AT, Nakaya HI |
Citation(s) |
32518143 |
Submission date |
Jan 24, 2019 |
Last update date |
Aug 18, 2020 |
Contact name |
Helder I. Nakaya |
E-mail(s) |
hnakaya@usp.br
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Organization name |
Universidade de São Paulo
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Street address |
438, Av. Prof. Lúcio Martins Rodrigues, 374 - Butantã
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City |
São Paulo |
ZIP/Postal code |
05508-020 |
Country |
Brazil |
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Platforms (1) |
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Samples (4)
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Relations |
BioProject |
PRJNA516806 |
SRA |
SRP181818 |
Supplementary file |
Size |
Download |
File type/resource |
GSE125554_zikv_counts.csv.gz |
323.1 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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