A human-derived 3D brain organoid model to study JC virus infection

Lade...
Vorschaubild
Dateien
Zu diesem Dokument gibt es keine Dateien.
Datum
2022
Autor:innen
Barreras, Paula
Pamies, David
Monaco, Maria Chiara
Muñoz, Laura S.
Zhong, Xiali
Major, Eugene O.
Hogberg, Helena T.
Pardo, Carlos A.
Herausgeber:innen
Kontakt
ISSN der Zeitschrift
Electronic ISSN
ISBN
Bibliografische Daten
Verlag
Schriftenreihe
Auflagebezeichnung
URI (zitierfähiger Link)
ArXiv-ID
Internationale Patentnummer
Angaben zur Forschungsförderung
Projekt
Open Access-Veröffentlichung
Sammlungen
Core Facility der Universität Konstanz
Gesperrt bis
Titel in einer weiteren Sprache
Forschungsvorhaben
Organisationseinheiten
Zeitschriftenheft
Publikationstyp
Zeitschriftenartikel
Publikationsstatus
Published
Erschienen in
Journal of neurovirology. Springer Nature. 2022, 28(1), pp. 17-26. ISSN 1355-0284. eISSN 1538-2443. Available under: doi: 10.1007/s13365-022-01062-7
Zusammenfassung

Progressive multifocal leukoencephalopathy (PML) is a frequent neurological complication in immunosuppressed patients. PML is caused by the JC virus (JCV), a neurotropic DNA polyomavirus that infects oligodendrocytes and astrocytes, causing inflammation and demyelination which lead to neurological dysfunction. The pathogenesis of PML is poorly understood due to the lack of in vitro or animal models to study mechanisms of disease as the virus most efficiently infects only human cells. We developed a human-derived brain organotypic system (also called brain organoid) to model JCV infection. The model was developed by using human-induced pluripotent stem cells (iPSC) and culturing them in 3D to generate an organotypic model containing neurons, astrocytes, and oligodendrocytes which recapitulates aspects of the environment of the human brain. We infected the brain organoids with the JCV MAD4 strain or cerebrospinal fluid of a patient with PML. The organoids were assessed for evidence of infection by qPCR, immunofluorescence, and electron microscopy at 1, 2, and 3 weeks post-exposure. JCV infection in both JCV MAD4 strain and PML CSF-exposed brain organoids was confirmed by immunocytochemical studies demonstrating viral antigens and electron microscopy showing virion particles in the nuclear compartment of oligodendrocytes and astrocytes. No evidence of neuronal infection was visualized. Infection was also demonstrated by JCV qPCR in the virus-exposed organoids and their media. In conclusion, the brain organoid model of JCV infection establishes a human model suitable for studying the mechanisms of JCV infection and pathogenesis of PML and may facilitate the exploration of therapeutic approaches.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
JCV · JC virus · Organoid · In vitro model · Human cells · Microphysiological system
Konferenz
Rezension
undefined / . - undefined, undefined
Zitieren
ISO 690BARRERAS, Paula, David PAMIES, Maria Chiara MONACO, Laura S. MUÑOZ, Xiali ZHONG, Eugene O. MAJOR, Helena T. HOGBERG, Thomas HARTUNG, Carlos A. PARDO, 2022. A human-derived 3D brain organoid model to study JC virus infection. In: Journal of neurovirology. Springer Nature. 2022, 28(1), pp. 17-26. ISSN 1355-0284. eISSN 1538-2443. Available under: doi: 10.1007/s13365-022-01062-7
BibTex
@article{Barreras2022-02human-57023,
  year={2022},
  doi={10.1007/s13365-022-01062-7},
  title={A human-derived 3D brain organoid model to study JC virus infection},
  number={1},
  volume={28},
  issn={1355-0284},
  journal={Journal of neurovirology},
  pages={17--26},
  author={Barreras, Paula and Pamies, David and Monaco, Maria Chiara and Muñoz, Laura S. and Zhong, Xiali and Major, Eugene O. and Hogberg, Helena T. and Hartung, Thomas and Pardo, Carlos A.}
}
RDF
<rdf:RDF
    xmlns:dcterms="http://purl.org/dc/terms/"
    xmlns:dc="http://purl.org/dc/elements/1.1/"
    xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"
    xmlns:bibo="http://purl.org/ontology/bibo/"
    xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#"
    xmlns:foaf="http://xmlns.com/foaf/0.1/"
    xmlns:void="http://rdfs.org/ns/void#"
    xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > 
  <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/57023">
    <dc:contributor>Zhong, Xiali</dc:contributor>
    <dc:contributor>Hartung, Thomas</dc:contributor>
    <dc:contributor>Monaco, Maria Chiara</dc:contributor>
    <dc:creator>Monaco, Maria Chiara</dc:creator>
    <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:creator>Hartung, Thomas</dc:creator>
    <dc:creator>Muñoz, Laura S.</dc:creator>
    <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/>
    <dc:language>eng</dc:language>
    <dc:contributor>Hogberg, Helena T.</dc:contributor>
    <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-28T15:17:14Z</dcterms:available>
    <dc:creator>Zhong, Xiali</dc:creator>
    <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/>
    <dc:contributor>Barreras, Paula</dc:contributor>
    <dc:contributor>Pardo, Carlos A.</dc:contributor>
    <dc:contributor>Pamies, David</dc:contributor>
    <dc:creator>Pamies, David</dc:creator>
    <dcterms:abstract xml:lang="eng">Progressive multifocal leukoencephalopathy (PML) is a frequent neurological complication in immunosuppressed patients. PML is caused by the JC virus (JCV), a neurotropic DNA polyomavirus that infects oligodendrocytes and astrocytes, causing inflammation and demyelination which lead to neurological dysfunction. The pathogenesis of PML is poorly understood due to the lack of in vitro or animal models to study mechanisms of disease as the virus most efficiently infects only human cells. We developed a human-derived brain organotypic system (also called brain organoid) to model JCV infection. The model was developed by using human-induced pluripotent stem cells (iPSC) and culturing them in 3D to generate an organotypic model containing neurons, astrocytes, and oligodendrocytes which recapitulates aspects of the environment of the human brain. We infected the brain organoids with the JCV MAD4 strain or cerebrospinal fluid of a patient with PML. The organoids were assessed for evidence of infection by qPCR, immunofluorescence, and electron microscopy at 1, 2, and 3 weeks post-exposure. JCV infection in both JCV MAD4 strain and PML CSF-exposed brain organoids was confirmed by immunocytochemical studies demonstrating viral antigens and electron microscopy showing virion particles in the nuclear compartment of oligodendrocytes and astrocytes. No evidence of neuronal infection was visualized. Infection was also demonstrated by JCV qPCR in the virus-exposed organoids and their media. In conclusion, the brain organoid model of JCV infection establishes a human model suitable for studying the mechanisms of JCV infection and pathogenesis of PML and may facilitate the exploration of therapeutic approaches.</dcterms:abstract>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2022-03-28T15:17:14Z</dc:date>
    <dc:creator>Major, Eugene O.</dc:creator>
    <dc:creator>Barreras, Paula</dc:creator>
    <dcterms:issued>2022-02</dcterms:issued>
    <dc:contributor>Muñoz, Laura S.</dc:contributor>
    <dc:contributor>Major, Eugene O.</dc:contributor>
    <dc:creator>Hogberg, Helena T.</dc:creator>
    <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/57023"/>
    <dcterms:title>A human-derived 3D brain organoid model to study JC virus infection</dcterms:title>
    <foaf:homepage rdf:resource="http://localhost:8080/"/>
    <dc:creator>Pardo, Carlos A.</dc:creator>
  </rdf:Description>
</rdf:RDF>
Interner Vermerk
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Kontakt
URL der Originalveröffentl.
Prüfdatum der URL
Prüfungsdatum der Dissertation
Finanzierungsart
Kommentar zur Publikation
Allianzlizenz
Corresponding Authors der Uni Konstanz vorhanden
Internationale Co-Autor:innen
Universitätsbibliographie
Ja
Begutachtet
Ja
Diese Publikation teilen