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Human Cytomegalovirus Infection Causes Premature and Abnormal Differentiation of Human Neural Progenitor Cells

ABSTRACT: Our results suggest that HCMV infection disrupts the self-renewal capacity of NPCs and influences their differentiation. Whole genome expression analysis revealed many changes in cellular gene expression, including downregulation of genes pertinent to the neuronal lineage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19345 | GEO | 2009/12/08

SECONDARY ACCESSION(S): PRJNA121723

REPOSITORIES: GEO

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Transcription profiling of human neural stem cell culture after infection with HCMV reveals HCMV infection disrupts the self-renewal capacity of neural progenitor cells and inhibits neuronal differentiation

Project description:Our results suggest that HCMV infection disrupts the self-renewal capacity of NPCs and influences their differentiation. Whole genome expression analysis revealed many changes in cellular gene expression, including downregulation of genes pertinent to the neuronal lineage. Experiment Overall Design: For gene expression analysis, cells were either mock- or virus-infected. Mock-infectedÂ cells were harvested at 12 hpi, virus infected cells were harvested at 4, 12 and 24 hpi. Virus- and mock-infections were performed in duplicate, with each individual sample harvested separately, thereby acting as biological replicates for analysis.

2009-12-14 | E-GEOD-19345 | biostudies-arrayexpress

Human induced pluripotent stem cell-technology to study the effects of human cytomegalovirus infection on neural differentiation

Project description:Congenital human cytomegalovirus (HCMV) infection is one of the leading prenatal causes of mental retardation and congenital deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV has been limited by difficulties in sustaining primary cultures. Neuronal cells derived from human induced pluripotent stem (iPS) cells now provide a novel opportunity to investigate HCMV pathogenesis. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their permissiveness to infection with HCMV strain Ad169. Analysis of iPS cells and nearly pure populations of iPS-derived neural stem cells (NSCs), neuroprogenitor cells (NPCs) and neurons suggests that (i) iPS cells are not permissive to HCMV infection; (ii) Neural stem cells have impaired differentiation when infected by HCMV; (iii) NPCs are fully permissive for HCMV infection; the supernatant from infected neural stem cells and NPCs (but not mock infected cells) induced cytopathic effects in human fibroblasts; (iv) most iPS-derived neurons are not permissive to HCMV infection; and (v) infected neurons have impaired calcium influx in response to glutamate. Our approach offers powerful cellular models to investigate the effect of neurotropic viral agents on human neurodevelopment. Adherent monolayer culture of neural progenitor cells (NPCs) were either infected with HCMV Ad169 in triplicate, with each individual sample harvested separately to provide biological replicates for expression analysis. Infected and mock-infected cells were harvested 24 h p.i. RNA. NPCs were 70-80% confluence.

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Project description:Congenital human cytomegalovirus (HCMV) infection is the leading infectious cause of birth defects, including neurodevelopmental disorders. HCMV infection mainly targets neural progenitor cells (NPCs) in fetal brains, inducing abnormal differentiation by altering key regulatory pathways. HCMV expresses a series of viral miRNAs during infection, but their roles, particularly in NPCs, are not fully understood. In this study, we characterized expression profiles of both cellular and viral miRNAs in HCMV-infected NPCs by microarray analysis during early infection time points and investigated the primary effects of these miRNAs on regulating NPC fate. While expression of most cellular miRNAs was unaffected by HCMV infection, one cellular miRNA was upregulated and six were downregulated from 2 to 24 h post infection. Moreover, of 17 HCMV miRNAs evaluated, six were differentially expressed in HCMV-infected NPCs during early infection time points.

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Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells.

Project description: Not available

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