SARS-CoV-2 S1 Protein Induces Endolysosome Dysfunction and Neuritic Dystrophy.

Autor:	Datta G; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Miller NM; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Halcrow PW; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Khan N; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Colwell T; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Geiger JD; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States., Chen X; Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular neuroscience [Front Cell Neurosci] 2021 Oct 27; Vol. 15, pp. 777738. Date of Electronic Publication: 2021 Oct 27 (Print Publication: 2021).
DOI:	10.3389/fncel.2021.777738
Abstrakt:	SARS-CoV-2 is the viral cause of the COVID-19 pandemic. Increasingly, significant neurological disorders have been associated with COVID-19. However, the pathogenesis of these neurological disorders remains unclear especially because only low or undetectable levels of SARS-CoV-2 have been reported in human brain specimens. Because SARS-CoV-2 S1 protein can be released from viral membranes, can cross the blood-brain barrier, and is present in brain cells including neurons, we tested the hypothesis that SARS-CoV-2 S1 protein can directly induce neuronal injury. Incubation of primary human cortical neurons with SARS-CoV-2 S1 protein resulted in accumulation of the S1 protein in endolysosomes as well as endolysosome de-acidification. Further, SARS-CoV-2 S1 protein induced aberrant endolysosome morphology and neuritic varicosities. Our findings suggest that SARS-CoV-2 S1 protein directly induces neuritic dystrophy, which could contribute to the high incidence of neurological disorders associated with COVID-19. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Datta, Miller, Halcrow, Khan, Colwell, Geiger and Chen.)
Databáze:	MEDLINE
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