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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Vydané v:	The EMBO journal Ročník 39; číslo 20; s. e106230 - n/a
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 15.10.2020 Springer Nature B.V EMBO Press John Wiley and Sons Inc
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work
ISSN:	0261-4189 1460-2075 1460-2075
DOI:	10.15252/embj.2020106230