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

Viruses
Sang Ah YiJaecheol Lee

Abstract

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.

References

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Citations

Nov 29, 2020·Biology Direct·Alexei VerkhratskyYufang Shi
Jan 7, 2021·Stem Cell Reviews and Reports·Irma Virant-Klun, Franc Strle
Feb 3, 2021·International Journal of Molecular Sciences·Henkie Isahwan Ahmad Mulyadi LaiYi-Ping Yang
Dec 11, 2020·Journal of Medical Virology·Brittany BodnarWenhui Hu
Mar 4, 2021·International Journal of Molecular Sciences·Marta TrevisanLuisa Barzon
May 9, 2021·Inflammation and Regeneration·Yoshitaka Kase, Hideyuki Okano
May 27, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jing-Han NgEng-King Tan

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Methods Mentioned

BETA
Infection
electrophoresis

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