GENETIC EVALUATION IN CONGENITAL ZIKA SYNDROME
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ABSTRACT:
PROVIDER: PRJEB40869 | ENA |
REPOSITORIES: ENA
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Project description:Congenital Zika syndrome (CZS), caused by Zika virus (ZIKV) infection, has been associated to impairment of early brain development, particularly related to neural progenitor cells (NPCs) survival and growth. In this work we report in a high-throughput manner (RNA-Seq) the differences in the transcriptomes of hiPSCs(human induced pluripotent stem cells)-derived NPCs from 3 pairs of discordant twins for Congenital Zika syndrome (CZS). We found significant differences in the expression levels of genes relevant to the regulation of neural development between the NPCs from CZS-affected and non-affected twins, suggesting that epigenetic differences may contribute to the different susceptibilities of NPCs to ZIKV infection.
2018-02-27 | GSE102128 | GEO
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).
2021-09-09 | PXD020294 | Pride
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.
2020-05-18 | GSE125554 | GEO
Project description:In this study, we analyzed by a shotgun proteomic approach the amniotic fluid of pregnant women infected with Zika carrying microcephalic (ZIKV+M+) or healthy fetuses (ZIKV+M-) compared to Zika negative controls (ZIKV-M-) to identify and understand the biological process and pathways affected by CZS development. Up-abundant proteins in the ZIKV+M- group showed enrichment mainly in the extracellular matrix (ECM) structure and organization. The innate immune system (i.e. neutrophil degranulation) and fibrin clot formation processes were dysregulated in the ZIKV+M+ group, with an increase in the abundance of proteins associated with these biological processes. In both groups, a decrease in the abundance of proteins associated with neutrophil degranulation was observed. ZIKV+M+ group presented a decrease of abundance in the dysregulated extracellular matrix proteins compared to ZIKV+M-. These results could suggest that the development of microcephalic or healthy phenotypes is more associated with the ECM and immune system protein abundances than the dysregulated processes in each group.
2024-07-02 | PXD023776 | Pride
Project description:During pregnancy, the Zika virus (ZIKV) can be vertically transmitted, causing Congenital Zika Syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances to develop CZS. This syndrome involves several pathologies with a difficult diagnosis, which usually occurs in the postnatal stage. In this work, we aim to identify biological processes and molecular pathways related to CZS development and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. Twenty-five serum samples of pregnant women were analyzed. For biological analysis, samples were separated into 3 biological groups composed of a control group of healthy pregnant women and two groups of ZIKV-infected pregnant women bearing non- microcephalic and microcephalic fetuses. Control and ZIKV-infected groups - without microcephalic fetuses - were subdivided into healthy and Cognitive Developmental Delay (CDD) newborns for biomarker analysis. We detected over 1,000 proteins and 500 metabolites by bottom-up proteomics and untargeted metabolomics, respectively. Statistical approaches - (t-Student, Limma, ANOVA, and DIABLO) - were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as signatures in the CZS development. Five proteins and four metabolites were selected as CZS biomarkers candidates. The protein-based model indicated superior performance values for the Vitamin K-dependent protein S, Selenoprotein P, Inter-alpha- trypsin inhibitor heavy chain H2, Kallistatin, and Protein Z-dependent protease inhibitor proteins. Furthermore, the metabolite-based model was able to predict CZS with a probability of 90%. Serum multi-omics analysis led us to propose for further studies nine potential biomarkers for CZS early prognosis with high sensitivity and specificity.
2024-07-02 | PXD043324 | Pride
Project description:Congenital hearing loss is a common chronic condition affecting children in both developed and developing nations. In many cases, congenital hearing loss is ultimately attributed to viral infection, most often by cytomegalovirus (CMV), but also in Congenital Zika Syndrome (CZS). The mechanisms by which CMV and ZIKV virus cause these cranial developmental defects have not been elucidated. Inner ear development has been particularly difficult to study, given the inaccessibility and scarcity of the tissue in animal models or on human autopsy; however, it is now possible to culture stem-cell derived otic progenitor cells (OPCs). Here we describe successful in-vitro infection of OPCs with either CMV or ZIKV. We find that ZIKV infection rapidly and strongly induces the expression of type I IFN and inflammatory genes, while simultaneously decreasing otic cell viability in culture that is at least in part attributable to apoptosis. In contrast, CMV infection did not appear to elicit either of these effects and instead demonstrated a clear dysregulation of the expression of many key genes and pathways associated with inner ear development and function, including Cochlin, NGFR, SOX11 and TGF-β signaling. These findings suggest that ZIKV and CMV infections cause congenital hearing loss through very different pathways; that is, by killing progenitor cells in the case of ZIKV infection, and via disruption of critical developmental pathways in the case of CMV infection. In addition to demonstrating differential hCMV and ZIKV pathogenesis mechanisms in OPCs, this study highlights the advantages of otic progenitor cell models for the study of congenital hearing loss induced by viral infection.
2024-01-18 | GSE234062 | GEO
Project description:Molecular Alterations of Extracellular Matrix in the Brain of Newborns with Congenital Zika Syndrome
| PRJNA516806 | ENA
Project description:Genome-wide DNA methylation profiling of over 850,000 methylation sites carried out using the Illumina MethylationEPIC BeadChip was used to compare 18 babies born with congenital Zika virus microcephaly, 7 babies exposed to Zika virus in utero but born without clinical signs, and 20 control unexposed unaffected babies
2020-07-20 | GSE145233 | GEO
Project description:BACKGROUND:Paralysis of the diaphragm in newborn infants can lead to recurrent infections and life-threatening respiratory insufficiency. The clinical diagnosis of unilateral diaphragmatic paralysis has been reported in infants with laboratory evidence of congenital Zika virus infection and/or the congenital Zika syndrome (CZS) phenotype but no evaluation of phrenic nerve function has been described. All reported infants have had accompanying arthrogryposis. High infant mortality is reported. METHODS:The causal mechanism of congenital diaphragmatic paralysis was evaluated in three infants with arthrogryposis as a manifestation of CZS (two of the three infants had laboratory evidence of ZIKV infection shortly after birth; the remaining infant had negative serology for ZIKV when first tested at 7 months of age). Electromyography and phrenic nerve compound muscle action potential (CMAP) were performed in all infants with diaphragmatic paralysis demonstrated on imaging studies. RESULTS:All infants had evidence of moderate chronic involvement of peripheral motor neurons. Phrenic nerve CMAP was reduced on the side of the diaphragmatic paralysis in two infants and reduced bilaterally in the remaining infant who had primarily anterior involvement of the diaphragm. All three infants had multiple medical complications and one infant died at 18?months of age. CONCLUSION:Evaluation of three infants with CZS and diaphragmatic paralysis demonstrated phrenic nerve dysfunction. In these and other affected infants, arthrogryposis appears to be a constant co-occurring condition and health problems are significant; both conditions are likely due to involvement of the peripheral nervous system in some infants with CZS.
| S-EPMC7197100 | biostudies-literature
Project description:Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. In this study, full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Nevertheless, these findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.
2019-10-22 | GSE139181 | GEO