@ARTICLE{10.3389/fncel.2021.777738, AUTHOR={Datta, Gaurav and Miller, Nicole M. and Halcrow, Peter W. and Khan, Nabab and Colwell, Timothy and Geiger, Jonathan D. and Chen, Xuesong}, TITLE={SARS-CoV-2 S1 Protein Induces Endolysosome Dysfunction and Neuritic Dystrophy}, JOURNAL={Frontiers in Cellular Neuroscience}, VOLUME={15}, YEAR={2021}, URL={https://www.frontiersin.org/articles/10.3389/fncel.2021.777738}, DOI={10.3389/fncel.2021.777738}, ISSN={1662-5102}, ABSTRACT={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.} }