Trial reportThe Journal of clinical investigation2014
Human glial chimeric mice reveal astrocytic dependence of JC virus infection.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- Beyond the neuron: the role of glial cells in viral neuropathogenesis.Journal of virology · 2026Review
- Long-term cerebral atrophy and cognitive function in patients recovering from progressive multifocal leukoencephalopathy: two case reports.BMC neurology · 2026Article
- Therapeutic potential of flavonols in the treatment of JCPyV.Microbiology spectrum · 2025Article
- Neurovascular pericytes are susceptible to infection by JC polyomavirus.Journal of virology · 2025Article
- Critical analysis of translational potential of rodent models of white matter pathology across a wide spectrum of human diseases.Cell death & disease · 2025Review
- Live long and persist: polyomavirus immune evasion in the brain and kidney.Future virology · 2025Article
- CRISPR antiviral inhibits neurotrophic JC polyomavirus in 2D and 3D culture models through dual-gRNA excision by SaCas9.Molecular therapy. Nucleic acids · 2025Article
- Amelioration of biased neuronal differentiation in humanized mouse model of valproic acid-induced autism by precisely targeted transcranial magnetic stimulation.Bioengineering & translational medicine · 2025Article
- Bridging the gaps between JCV infection models and human disease.Brain : a journal of neurology · 2024Article
- JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation.Brain : a journal of neurology · 2024Article
- Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy: A Multicenter Cohort Study.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Emerging Human Pluripotent Stem Cell-Based Human-Animal Brain Chimeras for Advancing Disease Modeling and Cell Therapy for Neurological Disorders.Neuroscience bulletin · 2024Review
- Article
- Polyomavirus Wakes Up and Chooses Neurovirulence.Viruses · 2023Review
- Revisiting JC virus and progressive multifocal leukoencephalopathy.Journal of neurovirology · 2023Review
- iPSC-derived three-dimensional brain organoid models and neurotropic viral infections.Journal of neurovirology · 2023Review
- Understanding polyomavirus CNS disease - a perspective from mouse models.The FEBS journal · 2022Review
- Microglia in antiviral immunity of the brain and spinal cord.Seminars in immunology · 2022Review
- A human-derived 3D brain organoid model to study JC virus infection.Journal of neurovirology · 2022Article
- Article
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease triggered by infection with the human gliotropic JC virus (JCV). Due to the human-selective nature of the virus, there are no animal models available to investigate JCV pathogenesis. To address this issue, we developed mice with humanized white matter by engrafting human glial progenitor cells (GPCs) into neonatal immunodeficient and myelin-deficient mice. Intracerebral delivery of JCV resulted in infection and subsequent demyelination of these chimeric mice. Human GPCs and astrocytes were infected more readily than oligodendrocytes, and viral replication was noted primarily in human astrocytes and GPCs rather than oligodendrocytes, which instead expressed early viral T antigens and exhibited apoptotic death. Engraftment of human GPCs in normally myelinated and immunodeficient mice resulted in humanized white matter that was chimeric for human astrocytes and GPCs. JCV effectively propagated in these mice, which indicates that astroglial infection is sufficient for JCV spread. Sequencing revealed progressive mutation of the JCV capsid protein VP1 after infection, suggesting that PML may evolve with active infection. These results indicate that the principal CNS targets for JCV infection are astrocytes and GPCs and that infection is associated with progressive mutation, while demyelination is a secondary occurrence, following T antigen-triggered oligodendroglial apoptosis. More broadly, this study provides a model by which to further assess the biology and treatment of human-specific gliotropic viruses.
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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.