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

Viruses

SangAh Yi¹  Dongmin Gim¹  Jihye Yun¹  Jeung-Whan Han¹  Daeho Joe¹  Jaecheol Lee¹  KiHong Nam¹  Han-Joo Kim²  YongHo Kim³ 

[1] Epigenome Dynamics Control Research Center, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea;Imnewrun Biosciences Inc., Suwon 16419, Korea;SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Korea;

关键词: SARS-CoV-2;    pseudovirus;    brain organoid;    cortical neuron;    ACE2;   

DOI  :  10.3390/v12091004

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown