Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids
Abstract Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem ce...
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BMC
2024-11-01
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Series: | Journal of Neuroinflammation |
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Online Access: | https://doi.org/10.1186/s12974-024-03275-5 |
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author | Christine Vazquez Seble G. Negatu Carl D. Bannerman Sowmya Sriram Guo-Li Ming Kellie A. Jurado |
author_facet | Christine Vazquez Seble G. Negatu Carl D. Bannerman Sowmya Sriram Guo-Li Ming Kellie A. Jurado |
author_sort | Christine Vazquez |
collection | DOAJ |
description | Abstract Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem cells, in particular radial glia, are basally primed to respond to virus infection by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with a neuropathogenic Enterovirus-D68 strain, demonstrated the ability of this virus to impede immune activation by blocking interferon responses. Together, our data highlight immune gene signatures present in different types of neural stem cells and differential viral capacity to block neural-specific immune induction. |
format | Article |
id | doaj-art-e300f8d4ec874862bf49f7c9afbf789c |
institution | Kabale University |
issn | 1742-2094 |
language | English |
publishDate | 2024-11-01 |
publisher | BMC |
record_format | Article |
series | Journal of Neuroinflammation |
spelling | doaj-art-e300f8d4ec874862bf49f7c9afbf789c2024-11-10T12:35:38ZengBMCJournal of Neuroinflammation1742-20942024-11-0121111710.1186/s12974-024-03275-5Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoidsChristine Vazquez0Seble G. Negatu1Carl D. Bannerman2Sowmya Sriram3Guo-Li Ming4Kellie A. Jurado5Department of Microbiology, University of Pennsylvania Perelman School of MedicineDepartment of Microbiology, University of Pennsylvania Perelman School of MedicineDepartment of Microbiology, University of Pennsylvania Perelman School of MedicineDepartment of Microbiology, University of Pennsylvania Perelman School of MedicineDepartment of Neuroscience, University of Pennsylvania Perelman School of MedicineDepartment of Microbiology, University of Pennsylvania Perelman School of MedicineAbstract Neural stem cells have intact innate immune responses that protect them from virus infection and cell death. Yet, viruses can antagonize such responses to establish neuropathogenesis. Using a forebrain organoid model system at two developmental time points, we identified that neural stem cells, in particular radial glia, are basally primed to respond to virus infection by upregulating several antiviral interferon-stimulated genes. Infection of these organoids with a neuropathogenic Enterovirus-D68 strain, demonstrated the ability of this virus to impede immune activation by blocking interferon responses. Together, our data highlight immune gene signatures present in different types of neural stem cells and differential viral capacity to block neural-specific immune induction.https://doi.org/10.1186/s12974-024-03275-5EV-D68Innate immunityCentral nervous systemForebrain organoidsNeuronsNeural stem cell |
spellingShingle | Christine Vazquez Seble G. Negatu Carl D. Bannerman Sowmya Sriram Guo-Li Ming Kellie A. Jurado Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids Journal of Neuroinflammation EV-D68 Innate immunity Central nervous system Forebrain organoids Neurons Neural stem cell |
title | Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids |
title_full | Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids |
title_fullStr | Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids |
title_full_unstemmed | Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids |
title_short | Antiviral immunity within neural stem cells distinguishes Enterovirus-D68 strain differences in forebrain organoids |
title_sort | antiviral immunity within neural stem cells distinguishes enterovirus d68 strain differences in forebrain organoids |
topic | EV-D68 Innate immunity Central nervous system Forebrain organoids Neurons Neural stem cell |
url | https://doi.org/10.1186/s12974-024-03275-5 |
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