ArticleHerpesviridae2013
Human cytomegalovirus induces apoptosis in neural stem/progenitor cells derived from induced pluripotent stem cells by generating mitochondrial dysfunction and endoplasmic reticulum stress.
Article in Herpesviridae, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Mitochondrial changes associated with viral infectious diseases in the paediatric population.Reviews in medical virology · 2021Pooled it
- Cytomegalovirus Infection Affects the Differentiation and Determines the Functionality of a Human Progenitor Neural Cell Line.Current microbiology · 2025Article
- Human induced pluripotent stem cells are resistant to human cytomegalovirus infection primarily at the attachment level due to the reduced expression of cell-surface heparan sulfate.Journal of virology · 2024Article
- HCMV Infection Reduces Nidogen-1 Expression, Contributing to Impaired Neural Rosette Development in Brain Organoids.Journal of virology · 2023Article
- HCMV-miR-US33-5p promotes apoptosis of aortic vascular smooth muscle cells by targeting EPAS1/SLC3A2 pathway.Cellular & molecular biology letters · 2022Article
- Using 2D and 3D pluripotent stem cell models to study neurotropic viruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- Vitamin D3 Suppresses Human Cytomegalovirus-Induced Vascular Endothelial ApoptosisFrontiers in microbiology · 2022Article
- Consequences of Viral Infection and Cytokine Production During Pregnancy on Brain Development in Offspring.Frontiers in immunology · 2022Review
- Neural Stem Cells: What Happens When They Go Viral?Viruses · 2021Review
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- Human Cytomegalovirus Compromises Development of Cerebral Organoids.Journal of virology · 2019Article
- Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells.Journal of virology · 2019Article
- Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models.Comprehensive physiology · 2019Review
- An iPSC-Derived Myeloid Lineage Model of Herpes Virus Latency and Reactivation.Frontiers in microbiology · 2019Article
- NOD1 and NOD2: Beyond Peptidoglycan Sensing.Trends in immunology · 2017Review
- Human cytomegalovirus downregulates SLITRK6 expression through IE2.Journal of neurovirology · 2017Article
- Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress.Cell death & disease · 2017Article
- New insights into the unfolded protein response in stem cells.Oncotarget · 2016Review
- PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCongenital human cytomegalovirus (HCMV) infection, a leading cause of birth defects, is most often manifested as neurological disorders. The pathogenesis of HCMV-induced neurological disorders is, however, largely unresolved, primarily because of limited availability of model systems to analyze the effects of HCMV infection on neural cells.
methodsAn induced pluripotent stem cell (iPSC) line was established from the human fibroblast line MRC5 by introducing the Yamanaka's four factors and then induced to differentiate into neural stem/progenitor cells (NSPCs) by dual inhibition of the SMAD signaling pathway using Noggin and SB-431542.
resultsiPSC-derived NSPCs (NSPC/iPSCs) were susceptible to HCMV infection and allowed the expression of both early and late viral gene products. HCMV-infected NSPC/iPSCs underwent apoptosis with the activation of caspase-3 and -9 as well as positive staining by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Cytochrome c release from mitochondria to cytosol was observed in these cells, indicating the involvement of mitochondrial dysfunction in their apoptosis. In addition, phosphorylation of proteins involved in the unfolded protein response (UPR), such as PKR-like eukaryotic initiation factor 2a kinase (PERK), c-Jun NH2-terminal kinase (JNK), inositol-requiring enzyme 1 (IRE1), and the alpha subunit of eukaryotic initiation factor 2 (eIF2α) was observed in HCMV-infected NSPC/iPSCs. These results, coupled with the finding of increased expression of mRNA encoding the C/EBP-homologous protein (CHOP) and the detection of a spliced form of X-box binding protein 1 (XBP1) mRNA, suggest that endoplasmic reticulum (ER) stress is also involved in HCMV-induced apoptosis of these cells.
conclusionsiPSC-derived NSPCs are thought to be a useful model to study HCMV neuropathogenesis and to analyze the mechanisms of HCMV-induced apoptosis in neural cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.