Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus

Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryon...

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Bibliographic Details
Published in:	Viruses Vol. 12; no. 9; p. 1004
Main Authors:	Yi, Sang Ah, Nam, Ki Hong, Yun, Jihye, Gim, Dongmin, Joe, Daeho, Kim, Yong Ho, Kim, Han-Joo, Han, Jeung-Whan, Lee, Jaecheol
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 08-09-2020 MDPI
Subjects:	ACE2 Angiotensin-Converting Enzyme 2 Antibodies Axons - enzymology Betacoronavirus - physiology brain organoid Brain stem Cell adhesion & migration Cell Differentiation Cells, Cultured Cerebral Cortex - cytology Coronaviruses cortical neuron COVID-19 Cytomegalovirus Embryonic Stem Cells - virology HEK293 Cells Humans Infections Infectivity Nerve Tissue Proteins - physiology Nervous system Neural stem cells Neural Stem Cells - enzymology Neural Stem Cells - virology Neurons Neurons - enzymology Neurons - virology Organoids Organoids - virology Peptidyl-Dipeptidase A - physiology Prosencephalon - cytology Prosencephalon - virology pseudovirus Receptors, Virus - physiology SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - physiology Stem cells Viral infections Viral Load Viral Tropism Virus Internalization United States > US cortical neuron ACE2 pseudovirus SARS-CoV-2 brain organoid
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Summary:	Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1999-4915 1999-4915
DOI:	10.3390/v12091004