{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:24:57Z","timestamp":1790763897405,"version":"4.1.0"},"reference-count":108,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme under the Marie Sklow-dowska-Curie Grant Agreement OrganoVIR","award":["812673"],"award-info":[{"award-number":["812673"]}]},{"name":"uniQure Biopharma B.V.","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Pathogenesis of viral infections of the central nervous system (CNS) is poorly understood, and this is partly due to the limitations of currently used preclinical models. Brain organoid models can overcome some of these limitations, as they are generated from human derived stem cells, differentiated in three dimensions (3D), and can mimic human neurodevelopmental characteristics. Therefore, brain organoids have been increasingly used as brain models in research on various viruses, such as Zika virus, severe acute respiratory syndrome coronavirus 2, human cytomegalovirus, and herpes simplex virus. Brain organoids allow for the study of viral tropism, the effect of infection on organoid function, size, and cytoarchitecture, as well as innate immune response; therefore, they provide valuable insight into the pathogenesis of neurotropic viral infections and testing of antivirals in a physiological model. In this review, we summarize the results of studies on viral CNS infection in brain organoids, and we demonstrate the broad application and benefits of using a human 3D model in virology research. At the same time, we describe the limitations of the studies in brain organoids, such as the heterogeneity in organoid generation protocols and age at infection, which result in differences in results between studies, as well as the lack of microglia and a blood brain barrier.<\/jats:p>","DOI":"10.3390\/v14030634","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:37:17Z","timestamp":1647812237000},"page":"634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Human Brain Organoids as Models for Central Nervous System Viral Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Josse A.","family":"Depla","sequence":"first","affiliation":[{"name":"OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Pediatric Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"UniQure Biopharma B.V., Department of Research & Development, Paasheuvelweg 25A, 1105 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance A.","family":"Mulder","sequence":"additional","affiliation":[{"name":"OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Pediatric Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-6115","authenticated-orcid":false,"given":"Renata Vieira","family":"de S\u00e1","sequence":"additional","affiliation":[{"name":"UniQure Biopharma B.V., Department of Research & Development, Paasheuvelweg 25A, 1105 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgane","family":"Wartel","sequence":"additional","affiliation":[{"name":"UniQure Biopharma B.V., Department of Research & Development, Paasheuvelweg 25A, 1105 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-4884","authenticated-orcid":false,"given":"Adithya","family":"Sridhar","sequence":"additional","affiliation":[{"name":"OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melvin M.","family":"Evers","sequence":"additional","affiliation":[{"name":"UniQure Biopharma B.V., Department of Research & Development, Paasheuvelweg 25A, 1105 BE Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-7049","authenticated-orcid":false,"given":"Katja C.","family":"Wolthers","sequence":"additional","affiliation":[{"name":"OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-8206","authenticated-orcid":false,"given":"Dasja","family":"Pajkrt","sequence":"additional","affiliation":[{"name":"OrganoVIR Labs, Department of Medical Microbiology, Amsterdam UMC Location Academic Medical Center, Amsterdam Institute for Infection and Immunity, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Pediatric Infectious Diseases, Emma Children\u2019s Hospital, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coviro.2014.12.009","article-title":"Viral Diseases of the Central Nervous System","volume":"11","author":"Swanson","year":"2015","journal-title":"Curr. 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