Ontology highlight
ABSTRACT:
PROVIDER: PRJNA573521 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Host and genetic viral adaptations enable development of an immunocompetent mouse model of Zika virus infection. This study explored the effect of wildtype Zika virus (ZIKV) and mouse adapted ZIKV infection on the transcriptional profile of mouse adult neuronal stem cells.
2018-04-05 | GSE112711 | GEO
Project description:A new mouse model for congenital Zika infection in a wildtype, immunocompetent background employing intraplacental infection resulted in productive infection of embryonic brains and features of microcephaly during early development (E10.5-16.5). Gross morphological characterization showed translational relevance for understanding the viral neuropathogenesis and Zika-associated microcephaly in humans. Thus, an integrated, multi-omics (RNA-sequencing, proteomics) analysis of fetal brain tissues was performed to understand pathways perturbed by viral infection in developing brains. These analyses identified virus-induced defects in cell cycle progression and neurodevelopment, in S-phase DNA replication and NEUROD2/TBR2 transcription factor cascades, respectively. Among the most significant responses was induction of innate immune programs in ZIKV-infected brains, including immunoproteasome activation and MHC-I antigen display associated with immune cell infiltration and neuronal death during early development. Identification of specific components within major pathways contributing to viral infection-induced effects on neurodevelopment provides novel targets for therapeutic intervention against neurotropic infections and ZIKV-associated microcephaly specifically.
2023-03-06 | MSV000091415 | MassIVE
Project description:A new mouse model for congenital Zika infection in a wildtype, immunocompetent background employing intraplacental infection resulted in productive infection of embryonic brains and features of microcephaly during early development (E10.5-16.5). Gross morphological characterization showed translational relevance for understanding the viral neuropathogenesis and Zika-associated microcephaly in humans. Thus, an integrated, multi-omics (RNA-sequencing, proteomics) analysis of fetal brain tissues was performed to understand pathways perturbed by viral infection in developing brains. These analyses identified virus-induced defects in cell cycle progression and neurodevelopment, in S-phase DNA replication and NEUROD2/TBR2 transcription factor cascades, respectively. Among the most significant responses was induction of innate immune programs in ZIKV-infected brains, including immunoproteasome activation and MHC-I antigen display associated with immune cell infiltration and neuronal death during early development. Identification of specific components within major pathways contributing to viral infection-induced effects on neurodevelopment provides novel targets for therapeutic intervention against neurotropic infections and ZIKV-associated microcephaly specifically.
2021-08-21 | GSE118935 | GEO
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:PolyA+ RNA sequencing of Zika virus-infected human brain organoids at 5 days post-infection.
2017-04-03 | E-MTAB-4811 | biostudies-arrayexpress
Project description:The re-emergence of Zika virus (ZIKV) in the Western Hemisphere has resulted in global public health crisis since 2015. ZIKV preferentially infects and targets human neural progenitor cells (hNPCs) and causes fetal microcephaly upon maternal infection. hNPCs not only play critical roles during fetal brain development, but also persist in adult brain throughout life. Yet the mechanism of innate antiviral immunity in hNPCs remains largely unknown. Here, we show that ZIKV infection triggers the abundant production of virus-derived small interfering RNAs in hNPCs, but not in the more differentiated progenies or somatic cells. Ablation of key RNAi machinery components significantly enhances ZIKV replication in hNPCs. Furthermore, enoxacin, a broad-spectrum antibiotic that is known as an RNAi enhancer, exerts potent anti-ZIKV activity in hNPCs and other RNAi-competent cells. Strikingly, enoxacin treatment completely prevents ZIKV infection and circumvents ZIKV-induced microcephalic phenotypes in brain organoid models that recapitulate human fetal brain development. Our findings highlight the physiological importance of RNAi-mediated antiviral immunity during the early stage of human brain development, uncovering a novel strategy to combat human congenital viral infections through enhancing RNAi.
2019-04-15 | GSE125520 | GEO
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 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) 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. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. Further investigation of ZIKV-host interactions based our transcriptomic datasets may help to illuminate neural virulence determinants of ZIKV in patients.
2016-08-23 | GSE80434 | GEO
Project description:To search for host factors regulating Zika virus infection, we performed a genome-wide loss-of-function CRISPR/Cas9 screen in haploid human ESCs. The regulators were identified by the quantification of enrichment of their mutant clones within a pooled loss-of-function library upon Zika virus infection.
2023-05-31 | E-MTAB-11945 | biostudies-arrayexpress
Project description:This paper shows that, whereas SOX2+ cells in HDB are highly susceptible to ZKV, SOX2+ primary GBM samples exhibit moderate to high resistance to infection. These datasets address the reasons for this difference, based on infection of primary patient GBM and human developing brain samples with mCherry Zika reporter virus, then FACS sorting the Zika-mCherry positive and negative fractions from each sample for bulk RNA-Sequencing. The primary finding of importance is that Zika resistant GBMs exhibit an immune signature reflecting high levels of infiltration by microglia which are present only in small numbers or absent altogether in human developing brain.
2022-09-08 | GSE178621 | GEO