ZIKV infection of a hiPSC-NPC line derived from a Congenital ZIKV Syndrome (CZS)-affected patient
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE279319 | GEO | 2025/09/30
REPOSITORIES: GEO
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Project description:Zika virus (ZIKV) is a mosquito-borne flavivirus consisting of historical African and epidemic-associated Asian lineages. The latter can access the central nervous system and causes microcephaly in the developing foetus through infection and depletion of neural stem and progenitor cells. The molecular mechanisms involved in this depletion response are grossly unknown for cells arising from CZS-affected children. Since 2017, the concept of employing ZIKV as oncolytic virotherapy against brain tumours has gained momentum. Oncolytic virotherapy exploits viruses that preferentially infect and destroy cancer cells via two distinct routes of therapeutic action. Following infection, intense viral replication induces oncolysis, releasing virions into the tumour microenvironment to infect neighbouring tumour cells. ZIKV induces an oncolytic event in infected pediatric brain tumour cells, but the molecular mechanisms involved in this response are grossly unknown. Here, we sought to investigate the molecular mechanisms underlying both the oncolytic and neuropathogenic responses of ZIKV infection in brain tumour and NPCs, respectively.
2025-04-23 | GSE277900 | GEO
Project description:To identify the various host factors involved in ZIKV infection, we compared the transcriptional profile for ZIKV-infected human first-trimester placenta trophoblast cell (HTR8) and glioblastoma astrocytoma (U251-MG). Our results demonstrated that the common IFN, inflammatory cytokine, and chemokine production were activated upon ZIKV infection of these two cell types while serval DEGs were enriched in distinct biological processes related to the characteristics of cell types. Our findings identified multiple host factors associated with ZIKV pathogenesis and potential treatment of congenital zika syndrome (CZS)
2023-06-07 | GSE234128 | GEO
Project description:Here we use a proteomic approach to study the role of the placenta in ZIKV-induced microcephaly and the mechanisms of ZIKV to cross the placental barrier. Samples were separated into three groups: an uninfected control group (ZIKV-CZS-), a group of placentas infected by ZIKV with normal neonates (ZIKV+CZS-), and a group of placentas infected by ZIKV that developed microcephaly in newborns (ZIKV+CZS+). Zika virus causes DNA damage and impairs gene expression and mRNA translation during infection of the placenta. Processes related to viral transcytosis, like endocytosis, autophagy and disruption of actin filament were also observed in CZS-infected placentas, which could lead to a higher virus infiltration. Unncontrolled maternal immune response as well as greater expression of cellular adhesion proteins in the decidua could lead to a disruption of tolerance during pregnancy and induction of neurological malformation of the neonates
2024-07-02 | PXD023777 | Pride
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: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:Zika virus (ZIKV), a re-emerging flavivirus is associated with devastating developmental and neurological disease outcomes particularly in infants infected in utero. Towards understanding the molecular underpinning of the unique ZIKV disease pathologies, numerous transcriptome-wide studies have been undertaken. Notably, these studies have overlooked the assimilation of RNA-seq analysis from ZIKV-infected patients with cell culture and cell model systems. We determined that ZIKV-infection in human lung adenocarcinoma A549 cells, mirrored both transcriptional and alternative splicing profiles from previously published RNA-seq data of peripheral blood mononuclear cells collected from pediatric patients during early, late acute, and convalescent phases of ZIKV infection. Our analyses show that ZIKV infection in cultured cells correlates with transcriptional changes in patients, while the overlap in alternative splicing profiles was not as extensive. Overall, our data indicate that cell culture model systems support dissection of select molecular changes detected in patients and established the foundation for future studies elucidating the biological implications of alternative splicing during ZIKV infection.
2024-08-02 | GSE265922 | GEO
Project description:Disrupted in Schizophrenia 1 (DISC1) is essential for neuronal development and has been implicated in various psychiatric disorders. However, its role in Zika virus (ZIKV) infection, particularly in congenital Zika syndrome (CZS) and ZIKV-induced long-term neurodevelopmental defects, remains unexplored. In this study, we demonstrate that DISC1 suppresses ZIKV infection in human placental and neuroglia cells, as well as in murine macrophages. DISC1 also limits ZIKV dissemination from peripheral tissues to key organs of mice, including the uterus, testis, and brain, thereby reducing fetal abortion rates and intrauterine growth restriction. Notably, DISC1 is associated with long-term ZIKV effects, including memory loss, reduced anxiety and depression, declines in sociability and social novelty. Mechanistically, DISC1 activates autophagy by enhancing AMPKα phosphorylation and reducing mTOR phosphorylation, protecting against ZIKV infection. Additionally, DISC1 interacts with LC3 to further activate autophagy, partially contributing to inhibit ZIKV infection. In conclusion, DISC1 plays a critical factor in controlling ZIKV infection and mitigating CZS and ZIKV-induced neurocognitive decline.
2025-02-17 | GSE289385 | GEO
Project description:ZIKV infection of a hiPSC-NPC line derived from a Congenital ZIKV Syndrome (CZS)-affected patient
| PRJNA1171847 | ENA
Project description:Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function remains elusive. Here we systematically profiled transcriptomes of human neural progenitor cells (hNPCs) and astrocytes exposed to Asian ZIKVC, African ZIKVM, and Dengue virus (DENV). DENV causes distinct gene expression changes; and ZIKV has a broader impact on the expression of gene involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes. Upon ZIKV infection, astrocytes exhibit more prominent transcriptome changes than hNPCs, particularly enriching genes related to inflammatory response and cytokine production pathways. Our analyses reveal cell-type- and strain-specific molecular signatures associated with ZIKV infection, and identify astrocytes as a major direct target of ZIKV. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients. Gene Expression Analyses of the cells infected with different flaviviruses
2016-08-23 | E-GEOD-80434 | biostudies-arrayexpress
Project description:Zika virus (ZIKV) can be transmitted vertically to the fetus, having a high chance to develop Congenital Zika Syndrome (CZS). Studies have shown that ZIKV impairs brain development. However, little is known about the molecular differences between non- microcephalic ZIKV-infected fetuses and microcephalic ones. Here, our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in ZIKV-infected patients and their relation to CZS progression. We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses. Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities. This study contributes to the understanding of CZS pathology and discovering potential biomarkers for CZS prognosis in the early stages of pregnancy.
2025-09-04 | PXD039643 | Pride