SARS‐CoV‐2 targets neurons of 3D human brain organoids

COVID‐19 pandemic caused by SARS‐CoV‐2 infection is a public health emergency. COVID‐19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS‐CoV‐2 on the central nervous system (CN...

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Published in:The EMBO journal Vol. 39; no. 20; pp. e106230 - n/a
Main Authors: Ramani, Anand, Müller, Lisa, Ostermann, Philipp N, Gabriel, Elke, Abida‐Islam, Pranty, Müller‐Schiffmann, Andreas, Mariappan, Aruljothi, Goureau, Olivier, Gruell, Henning, Walker, Andreas, Andrée, Marcel, Hauka, Sandra, Houwaart, Torsten, Dilthey, Alexander, Wohlgemuth, Kai, Omran, Heymut, Klein, Florian, Wieczorek, Dagmar, Adams, Ortwin, Timm, Jörg, Korth, Carsten, Schaal, Heiner, Gopalakrishnan, Jay
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 15.10.2020
Springer Nature B.V
EMBO Press
John Wiley and Sons Inc
Subjects:
Abnormalities
Animals
Axons
Betacoronavirus - physiology
Brain
Brain - virology
brain organoids
Cell Death
Central nervous system
Chlorocebus aethiops
Coronaviruses
COVID-19
EMBO23
EMBO24
EMBO27
Exposure
Humans
Life Sciences
Nervous system
Nervous System Diseases - virology
Neuroimaging
Neurons
Neurons - virology
Neurotoxicity
Organoids
Pandemics
Phosphorylation
Public health
SARS-CoV-2
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Tau pathology
Tau protein
tau Proteins - metabolism
Tropism
Vero Cells
Viral diseases
Tau pathology
brain organoids
cell death
SARS‐CoV-2
neurons
SARS-CoV-2
ISSN:0261-4189, 1460-2075, 1460-2075
Online Access:Get full text
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Summary:COVID‐19 pandemic caused by SARS‐CoV‐2 infection is a public health emergency. COVID‐19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS‐CoV‐2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS‐CoV‐2 enters 3D human brain organoids within 2 days of exposure. We identified that SARS‐CoV‐2 preferably targets neurons of brain organoids. Imaging neurons of organoids reveal that SARS‐CoV‐2 exposure is associated with altered distribution of Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Our studies, therefore, provide initial insights into the potential neurotoxic effect of SARS‐CoV‐2 and emphasize that brain organoids could model CNS pathologies of COVID‐19. Synopsis Modelling coronavirus exposure of the central nervous system is critical to assess the cellular tropism and potential neurological consequences of infection. Here, a Düsseldorf isolate of SARS‐CoV‐2 is shown to enter human cerebral organoids and preferably target neuronal cells. Clinical SARS‐CoV-2 strain targets neurons of 3D human brain organoids. SARS‐CoV-2 does not appear to actively proliferate in neurons. SARS‐CoV-2 is associated with Tau abnormalities in neurons. SARS‐CoV-2 induces neuronal cell death. Graphical Abstract In vitro exposure of cerebral organoids to coronavirus results in preferential infection and cell death of neuronal cells.
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These authors contributed equally to this work
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.15252/embj.2020106230