The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice.
Nat Neurosci
; 24(3): 368-378, 2021 03.
Article
in English
| MEDLINE | ID: covidwho-983666
ABSTRACT
It is unclear whether severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, can enter the brain. Severe acute respiratory syndrome coronavirus 2 binds to cells via the S1 subunit of its spike protein. We show that intravenously injected radioiodinated S1 (I-S1) readily crossed the blood-brain barrier in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by the lung, spleen, kidney and liver. Intranasally administered I-S1 also entered the brain, although at levels roughly ten times lower than after intravenous administration. APOE genotype and sex did not affect whole-brain I-S1 uptake but had variable effects on uptake by the olfactory bulb, liver, spleen and kidney. I-S1 uptake in the hippocampus and olfactory bulb was reduced by lipopolysaccharide-induced inflammation. Mechanistic studies indicated that I-S1 crosses the blood-brain barrier by adsorptive transcytosis and that murine angiotensin-converting enzyme 2 is involved in brain and lung uptake, but not in kidney, liver or spleen uptake.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Blood-Brain Barrier
/
Spike Glycoprotein, Coronavirus
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Nat Neurosci
Journal subject:
Neurology
Year:
2021
Document Type:
Article
Affiliation country:
S41593-020-00771-8
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