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Article

Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells

by 1,2,†, 1,†, 1,2,†, 1,3,†, 1 and 1,*
1
Neuroimmunology Laboratory, Dementia Research Group, Korea Brain Research Institute, Sinseo, Daegu 41062, Korea
2
Department of Brain & Cognitive Sciences, DGIST, Daegu 42988, Korea
3
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, 16 De Crespigny Park, London SE5 8AF, UK
*
Author to whom correspondence should be addressed.
These authors equally contributed.
Academic Editor: Yong-Hui Zheng
Viruses 2021, 13(10), 2021; https://doi.org/10.3390/v13102021
Received: 18 August 2021 / Revised: 19 September 2021 / Accepted: 1 October 2021 / Published: 8 October 2021
(This article belongs to the Section SARS-CoV-2 and COVID-19)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain. View Full-Text
Keywords: COVID-19; SARS-CoV-2; BBB; endothelial cells; metabolism COVID-19; SARS-CoV-2; BBB; endothelial cells; metabolism
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MDPI and ACS Style

Kim, E.S.; Jeon, M.-T.; Kim, K.-S.; Lee, S.; Kim, S.; Kim, D.-G. Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells. Viruses 2021, 13, 2021. https://doi.org/10.3390/v13102021

AMA Style

Kim ES, Jeon M-T, Kim K-S, Lee S, Kim S, Kim D-G. Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells. Viruses. 2021; 13(10):2021. https://doi.org/10.3390/v13102021

Chicago/Turabian Style

Kim, Eun S., Min-Tae Jeon, Kyu-Sung Kim, Suji Lee, Suji Kim, and Do-Geun Kim. 2021. "Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells" Viruses 13, no. 10: 2021. https://doi.org/10.3390/v13102021

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