tetano
Editor, Senior Moderator
Nat Neurosci
. 2020 Dec 16.
doi: 10.1038/s41593-020-00771-8. Online ahead of print.
The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice
Elizabeth M Rhea[SUP] 1 2 [/SUP], Aric F Logsdon[SUP] 1 2 [/SUP], Kim M Hansen[SUP] 1 2 [/SUP], Lindsey M Williams[SUP] 1 [/SUP], May J Reed[SUP] 2 [/SUP], Kristen K Baumann[SUP] 1 [/SUP], Sarah J Holden[SUP] 3 [/SUP], Jacob Raber[SUP] 3 4 [/SUP], William A Banks[SUP] 5 6 [/SUP], Michelle A Erickson[SUP] 1 2 [/SUP]
Affiliations
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.
. 2020 Dec 16.
doi: 10.1038/s41593-020-00771-8. Online ahead of print.
The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice
Elizabeth M Rhea[SUP] 1 2 [/SUP], Aric F Logsdon[SUP] 1 2 [/SUP], Kim M Hansen[SUP] 1 2 [/SUP], Lindsey M Williams[SUP] 1 [/SUP], May J Reed[SUP] 2 [/SUP], Kristen K Baumann[SUP] 1 [/SUP], Sarah J Holden[SUP] 3 [/SUP], Jacob Raber[SUP] 3 4 [/SUP], William A Banks[SUP] 5 6 [/SUP], Michelle A Erickson[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33328624
- DOI: 10.1038/s41593-020-00771-8
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.