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SARS-CoV-2 的 S1 蛋白可穿越血脑屏障进入小鼠脑内。

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

机构信息

Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.

Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.

出版信息

Nat Neurosci. 2021 Mar;24(3):368-378. doi: 10.1038/s41593-020-00771-8. Epub 2020 Dec 16.

DOI:10.1038/s41593-020-00771-8
PMID:33328624
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8793077/
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.

摘要

目前尚不清楚导致 2019 年冠状病毒病的严重急性呼吸综合征冠状病毒 2 是否能够进入大脑。严重急性呼吸综合征冠状病毒 2 通过其刺突蛋白的 S1 亚单位与细胞结合。我们发现，静脉注射的放射性碘标记 S1（I-S1）可轻易穿过雄性小鼠的血脑屏障，被大脑区域摄取并进入实质脑空间。I-S1 还被肺、脾、肾和肝摄取。鼻内给予的 I-S1 也进入了大脑，尽管其水平比静脉注射低大约十倍。载脂蛋白 E 基因型和性别对全脑 I-S1 摄取没有影响，但对嗅球、肝、脾和肾的摄取有不同的影响。脂多糖诱导的炎症会降低海马体和嗅球的 I-S1 摄取。机制研究表明，I-S1 通过吸附性转胞吞作用穿过血脑屏障，并且鼠血管紧张素转换酶 2 参与脑和肺摄取，但不参与肾、肝或脾摄取。

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