The potential role of the collagen gene family in congenital Zika syndrome: A systems biology approach
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Brain
DISEASE(S): Zika Virus Congenital Syndrome
SUBMITTER: 
Proteomics Unit
LAB HEAD: Fabio Nogueira
PROVIDER: PXD012461 | Pride | 2020-05-26
REPOSITORIES: Pride
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Data.pep.xml | Pepxml | |||
| FabioCSN_50001_3-01.msf | Msf | |||
| FabioCSN_50001_3.raw | Raw | |||
| FabioCSN_50001_4.raw | Raw | |||
| FabioCSN_50001_5.raw | Raw |
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Project description: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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Project description:In 2015, ZIKV infection attracted international attention during an epidemic in the Americas, when neurological disorders were reported in babies who had their mothers exposed to ZIKV during pregnancy. World Health Organization (WHO) epidemiological data show that 5 to 15% of neonates exposed to ZIKV in the uterus have complications included in abnormalities related to Congenital Zika Syndrome (CZS). The risk of complications after birth is not well documented, however, clinical evidence shows that 6% of babies exposed to ZIKV during pregnancy have complications present at birth, and this rate rises to 14% when medical monitoring is performed in all exposed babies, regardless of birth condition. Thus, the evaluation and monitoring of all exposed babies are of foremost importance as the development of late complications has been increasingly supported by clinical evidence. The identification of molecular markers in infants exposed to ZIKV without CZS could provide valuable means to improve their clinical monitoring. Here, we used a shotgun-proteomic approach to investigate molecular markers in the serum of infants without CZS symptoms but exposed to ZIKV intrauterine (ZIKV) compared to non-exposed controls (CTRL).
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Project description:BackgroundThe signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome.Methods and findingsA systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age.ConclusionsZika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.
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