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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Main Authors: Christine Vazquez, Seble G. Negatu, Carl D. Bannerman, Sowmya Sriram, Guo-Li Ming, Kellie A. Jurado
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Journal of Neuroinflammation
Subjects:
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.
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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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