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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Vydáno v:	The EMBO journal Ročník 39; číslo 20; s. e106230 - n/a
Hlavní autoři:	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:	angličtina
Vydáno:	London Nature Publishing Group UK 15.10.2020 Springer Nature B.V EMBO Press John Wiley and Sons Inc
Témata:	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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Abstract	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.
AbstractList	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. 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. In vitro exposure of cerebral organoids to coronavirus results in preferential infection and cell death of neuronal cells. 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. In vitro exposure of cerebral organoids to coronavirus results in preferential infection and cell death of neuronal cells. 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. 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. 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.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.
Author	Omran, Heymut Ostermann, Philipp N Korth, Carsten Gruell, Henning Gopalakrishnan, Jay Timm, Jörg Schaal, Heiner Dilthey, Alexander Mariappan, Aruljothi Müller‐Schiffmann, Andreas Wieczorek, Dagmar Andrée, Marcel Ramani, Anand Walker, Andreas Abida‐Islam, Pranty Hauka, Sandra Wohlgemuth, Kai Gabriel, Elke Houwaart, Torsten Müller, Lisa Adams, Ortwin Klein, Florian Goureau, Olivier
AuthorAffiliation	2 Institute of Virology Medical Faculty University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany 6 Institute of Medical Microbiology and Hygiene University Hospital Heinrich‐Heine‐University Düsseldorf Düsseldorf Germany 7 Department of General Pediatrics University Children's Hospital Muenster Muenster Germany 9 Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany 4 Institut de la Vision Sorbonne Université INSERM CNRS Paris France 8 German Center for Infection Research (DZIF) partner site Bonn‐Cologne Cologne Germany 5 Institute of Virology Faculty of Medicine University Hospital Cologne University of Cologne Cologne Germany 1 Institute of Human Genetics University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany 3 Institute of Neuropathology University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany
AuthorAffiliation_xml	– name: 4 Institut de la Vision Sorbonne Université INSERM CNRS Paris France – name: 6 Institute of Medical Microbiology and Hygiene University Hospital Heinrich‐Heine‐University Düsseldorf Düsseldorf Germany – name: 9 Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany – name: 3 Institute of Neuropathology University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany – name: 2 Institute of Virology Medical Faculty University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany – name: 8 German Center for Infection Research (DZIF) partner site Bonn‐Cologne Cologne Germany – name: 5 Institute of Virology Faculty of Medicine University Hospital Cologne University of Cologne Cologne Germany – name: 7 Department of General Pediatrics University Children's Hospital Muenster Muenster Germany – name: 1 Institute of Human Genetics University Hospital Düsseldorf Heinrich‐Heine‐Universität Düsseldorf Germany
Author_xml	– sequence: 1 givenname: Anand orcidid: 0000-0002-2380-8649 surname: Ramani fullname: Ramani, Anand organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 2 givenname: Lisa orcidid: 0000-0002-0728-0012 surname: Müller fullname: Müller, Lisa organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 3 givenname: Philipp N surname: Ostermann fullname: Ostermann, Philipp N organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 4 givenname: Elke surname: Gabriel fullname: Gabriel, Elke organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 5 givenname: Pranty surname: Abida‐Islam fullname: Abida‐Islam, Pranty organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 6 givenname: Andreas surname: Müller‐Schiffmann fullname: Müller‐Schiffmann, Andreas organization: Institute of Neuropathology, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 7 givenname: Aruljothi orcidid: 0000-0001-5286-9806 surname: Mariappan fullname: Mariappan, Aruljothi organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 8 givenname: Olivier surname: Goureau fullname: Goureau, Olivier organization: Institut de la Vision, Sorbonne Université, INSERM, CNRS – sequence: 9 givenname: Henning orcidid: 0000-0002-0725-7138 surname: Gruell fullname: Gruell, Henning organization: Institute of Virology, Faculty of Medicine, University Hospital Cologne, University of Cologne – sequence: 10 givenname: Andreas surname: Walker fullname: Walker, Andreas organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 11 givenname: Marcel surname: Andrée fullname: Andrée, Marcel organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 12 givenname: Sandra surname: Hauka fullname: Hauka, Sandra organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 13 givenname: Torsten surname: Houwaart fullname: Houwaart, Torsten organization: Institute of Medical Microbiology and Hygiene, University Hospital, Heinrich‐Heine‐University Düsseldorf – sequence: 14 givenname: Alexander surname: Dilthey fullname: Dilthey, Alexander organization: Institute of Medical Microbiology and Hygiene, University Hospital, Heinrich‐Heine‐University Düsseldorf – sequence: 15 givenname: Kai orcidid: 0000-0003-4092-0664 surname: Wohlgemuth fullname: Wohlgemuth, Kai organization: Department of General Pediatrics, University Children's Hospital Muenster – sequence: 16 givenname: Heymut orcidid: 0000-0003-0282-6765 surname: Omran fullname: Omran, Heymut organization: Department of General Pediatrics, University Children's Hospital Muenster – sequence: 17 givenname: Florian surname: Klein fullname: Klein, Florian organization: Institute of Virology, Faculty of Medicine, University Hospital Cologne, University of Cologne, German Center for Infection Research (DZIF), partner site Bonn‐Cologne, Center for Molecular Medicine Cologne (CMMC), University of Cologne – sequence: 18 givenname: Dagmar surname: Wieczorek fullname: Wieczorek, Dagmar organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 19 givenname: Ortwin surname: Adams fullname: Adams, Ortwin organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 20 givenname: Jörg surname: Timm fullname: Timm, Jörg organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 21 givenname: Carsten surname: Korth fullname: Korth, Carsten organization: Institute of Neuropathology, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 22 givenname: Heiner orcidid: 0000-0002-1636-4365 surname: Schaal fullname: Schaal, Heiner email: schaal@uni-duesseldorf.de organization: Institute of Virology, Medical Faculty, University Hospital Düsseldorf, Heinrich‐Heine‐Universität – sequence: 23 givenname: Jay orcidid: 0000-0002-0639-8705 surname: Gopalakrishnan fullname: Gopalakrishnan, Jay email: jay.gopalakrishnan@hhu.de organization: Institute of Human Genetics, University Hospital Düsseldorf, Heinrich‐Heine‐Universität
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32876341$$D View this record in MEDLINE/PubMed https://hal.science/hal-02969415$$DView record in HAL
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Snippet	COVID‐19 pandemic caused by SARS‐CoV‐2 infection is a public health emergency. COVID‐19 typically exhibits respiratory illness. Unexpectedly, emerging clinical... COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical...
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SubjectTerms	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
Title	SARS‐CoV‐2 targets neurons of 3D human brain organoids
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