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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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Autores principales: Yi, Sang Ah, Nam, Ki Hong, Yun, Jihye, Gim, Dongmin, Joe, Daeho, Kim, Yong Ho, Kim, Han-Joo, Han, Jeung-Whan, Lee, Jaecheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551632/
https://www.ncbi.nlm.nih.gov/pubmed/32911874
http://dx.doi.org/10.3390/v12091004
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author Yi, Sang Ah
Nam, Ki Hong
Yun, Jihye
Gim, Dongmin
Joe, Daeho
Kim, Yong Ho
Kim, Han-Joo
Han, Jeung-Whan
Lee, Jaecheol
author_facet Yi, Sang Ah
Nam, Ki Hong
Yun, Jihye
Gim, Dongmin
Joe, Daeho
Kim, Yong Ho
Kim, Han-Joo
Han, Jeung-Whan
Lee, Jaecheol
author_sort Yi, Sang Ah
collection PubMed
description 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.
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spelling pubmed-75516322020-10-14 Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus Yi, Sang Ah Nam, Ki Hong Yun, Jihye Gim, Dongmin Joe, Daeho Kim, Yong Ho Kim, Han-Joo Han, Jeung-Whan Lee, Jaecheol Viruses Article 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. MDPI 2020-09-08 /pmc/articles/PMC7551632/ /pubmed/32911874 http://dx.doi.org/10.3390/v12091004 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yi, Sang Ah
Nam, Ki Hong
Yun, Jihye
Gim, Dongmin
Joe, Daeho
Kim, Yong Ho
Kim, Han-Joo
Han, Jeung-Whan
Lee, Jaecheol
Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title_full Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title_fullStr Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title_full_unstemmed Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title_short Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus
title_sort infection of brain organoids and 2d cortical neurons with sars-cov-2 pseudovirus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551632/
https://www.ncbi.nlm.nih.gov/pubmed/32911874
http://dx.doi.org/10.3390/v12091004
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