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Tytuł pozycji:

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

Tytuł:
Infection of Brain Organoids and 2D Cortical Neurons with SARS-CoV-2 Pseudovirus.
Autorzy:
Yi SA; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Nam KH; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Yun J; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Gim D; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Joe D; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Kim YH; SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Korea.; Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Korea.; Department of Nano Engineering, Sungkyunkwan University, Suwon 16419, Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.; Imnewrun Biosciences Inc., Suwon 16419, Korea.
Kim HJ; Imnewrun Biosciences Inc., Suwon 16419, Korea.
Han JW; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Lee J; Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.; Imnewrun Biosciences Inc., Suwon 16419, Korea.
Źródło:
Viruses [Viruses] 2020 Sep 08; Vol. 12 (9). Date of Electronic Publication: 2020 Sep 08.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI
MeSH Terms:
Betacoronavirus/*physiology
Neurons/*virology
Organoids/*virology
Prosencephalon/*virology
Spike Glycoprotein, Coronavirus/*physiology
Angiotensin-Converting Enzyme 2 ; Axons/enzymology ; Cell Differentiation ; Cells, Cultured ; Cerebral Cortex/cytology ; Embryonic Stem Cells/virology ; HEK293 Cells ; Humans ; Nerve Tissue Proteins/physiology ; Neural Stem Cells/enzymology ; Neural Stem Cells/virology ; Neurons/enzymology ; Peptidyl-Dipeptidase A/physiology ; Prosencephalon/cytology ; Receptors, Virus/physiology ; SARS-CoV-2 ; Viral Load ; Viral Tropism ; Virus Internalization
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Contributed Indexing:
Keywords: ACE2; SARS-CoV-2; brain organoid; cortical neuron; pseudovirus
Substance Nomenclature:
0 (Nerve Tissue Proteins)
0 (Receptors, Virus)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
EC 3.4.15.1 (Peptidyl-Dipeptidase A)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
Entry Date(s):
Date Created: 20200911 Date Completed: 20200928 Latest Revision: 20201218
Update Code:
20240105
PubMed Central ID:
PMC7551632
DOI:
10.3390/v12091004
PMID:
32911874
Czasopismo naukowe
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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