ApoE-Isoform-Dependent SARS-CoV-2 Neurotropism and Cellular Response.
Cell Stem Cell
; 28(2): 331-342.e5, 2021 02 04.
Article
in English
| MEDLINE | ID: covidwho-1009887
ABSTRACT
ApoE4, a strong genetic risk factor for Alzheimer disease, has been associated with increased risk for severe COVID-19. However, it is unclear whether ApoE4 alters COVID-19 susceptibility or severity, and the role of direct viral infection in brain cells remains obscure. We tested the neurotropism of SARS-CoV2 in human-induced pluripotent stem cell (hiPSC) models and observed low-grade infection of neurons and astrocytes that is boosted in neuron-astrocyte co-cultures and organoids. We then generated isogenic ApoE3/3 and ApoE4/4 hiPSCs and found an increased rate of SARS-CoV-2 infection in ApoE4/4 neurons and astrocytes. ApoE4 astrocytes exhibited enlarged size and elevated nuclear fragmentation upon SARS-CoV-2 infection. Finally, we show that remdesivir treatment inhibits SARS-CoV2 infection of hiPSC neurons and astrocytes. These findings suggest that ApoE4 may play a causal role in COVID-19 severity. Understanding how risk factors impact COVID-19 susceptibility and severity will help us understand the potential long-term effects in different patient populations.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Apolipoproteins E
/
Brain
/
Tropism
/
Induced Pluripotent Stem Cells
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Cell Stem Cell
Year:
2021
Document Type:
Article
Affiliation country:
J.stem.2020.12.018
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