ArticleSchizophrenia bulletin2015
Persistent infection by HSV-1 is associated with changes in functional architecture of iPSC-derived neurons and brain activation patterns underlying working memory performance.
Article in Schizophrenia bulletin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- From viral epigenetic reprogramming to neuroinflammation: Mechanisms driving neurodegeneration.Journal of neurovirology · 2026Review
- From microstates to macroscales: A Critical Review of Maximum Entropy Modeling and Energy Landscape Analysis in functional MRI.Research square · 2025Article
- Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence.International journal of molecular sciences · 2025Review
- Independence-based causal discovery analysis reveals statistically non-significant regions to be functionally significant.bioRxiv : the preprint server for biology · 2025Article
- Ex vivo study of neuroinvasive and neurotropic viruses: what is current and what is next.FEMS microbiology reviews · 2025Review
- RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection.Journal of neurovirology · 2024Article
- Indicators of HSV1 Infection, ECM-Receptor Interaction, and Chromatin Modulation in a Nuclear Family with Schizophrenia.Journal of personalized medicine · 2023Article
- Therapeutic Implications of the Microbial Hypothesis of Mental Illness.Current topics in behavioral neurosciences · 2023Review
- Variations in Aspects of Neural Precursor Cell Neurogenesis in a Human Model of HSV-1 Infection.Organogenesis · 2022Article
- The Impaired Neurodevelopment of Human Neural Rosettes in HSV-1-Infected Early Brain Organoids.Cells · 2022Article
- Using 2D and 3D pluripotent stem cell models to study neurotropic viruses.Frontiers in virology (Lausanne, Switzerland) · 2022Article
- Disrupting Neurons and Glial Cells Oneness in the Brain-The Possible Causal Role of Herpes Simplex Virus Type 1 (HSV-1) in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons-A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction.International journal of molecular sciences · 2021Article
- Herpes Simplex Virus 1 and 2 Infections during Differentiation of Human Cortical Neurons.Viruses · 2021Article
- Review
- Patterns of Herpes Simplex Virus 1 Infection in Neural Progenitor Cells.Journal of virology · 2020Article
- Herpes Simplex Virus Latency Is Noisier the Closer We Look.Journal of virology · 2020Review
- Cell Line Models for Human Cytomegalovirus Latency Faithfully Mimic Viral Entry by Macropinocytosis and Endocytosis.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
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundHerpes simplex virus, type 1 (HSV-1) commonly produces lytic mucosal lesions. It invariably initiates latent infection in sensory ganglia enabling persistent, lifelong infection. Acute HSV-1 encephalitis is rare and definitive evidence of latent infection in the brain is lacking. However, exposure untraceable to encephalitis has been repeatedly associated with impaired working memory and executive functions, particularly among schizophrenia patients.
methodsPatterns of HSV-1 infection and gene expression changes were examined in human induced pluripotent stem cell (iPSC)-derived neurons. Separately, differences in blood oxygenation level-dependent (BOLD) responses to working memory challenges using letter n-back tests were investigated using functional magnetic resonance imaging (fMRI) among schizophrenia cases/controls.
resultsHSV-1 induced lytic changes in iPSC-derived glutamatergic neurons and neuroprogenitor cells. In neurons, HSV-1 also entered a quiescent state following coincubation with antiviral drugs, with distinctive changes in gene expression related to functions such as glutamatergic signaling. In the fMRI studies, main effects of schizophrenia (P = .001) and HSV-1 exposure (1-back, P = 1.76 × 10(-4); 2-back, P = 1.39 × 10(-5)) on BOLD responses were observed. We also noted increased BOLD responses in the frontoparietal, thalamus, and midbrain regions among HSV-1 exposed schizophrenia cases and controls, compared with unexposed persons.
conclusionsThe lytic/quiescent cycles in iPSC-derived neurons indicate that persistent neuronal infection can occur, altering cellular function. The fMRI studies affirm the associations between nonencephalitic HSV-1 infection and functional brain changes linked with working memory impairment. The fMRI and iPSC studies together provide putative mechanisms for the cognitive impairments linked to HSV-1 exposure.
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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.