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The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice

It is unclear whether SARS-CoV-2, which causes COVID-19, can enter the brain. SARS-CoV-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 (BBB) in male mice, was taken up by brain regions and...

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Detalles Bibliográficos
Autores principales: Rhea, Elizabeth M., Logsdon, Aric F., Hansen, Kim M., Williams, Lindsey M., Reed, May J., Baumann, Kristen K., Holden, Sarah J., Raber, Jacob, Banks, William A., Erickson, Michelle A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8793077/
https://www.ncbi.nlm.nih.gov/pubmed/33328624
http://dx.doi.org/10.1038/s41593-020-00771-8
Descripción
Sumario:It is unclear whether SARS-CoV-2, which causes COVID-19, can enter the brain. SARS-CoV-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 (BBB) in male mice, was taken up by brain regions and entered the parenchymal brain space. I-S1 was also taken up by lung, spleen, kidney, and liver. Intranasally administered I-S1 also entered the brain, though at ~10 times lower levels 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 BBB 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.