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.
【저자키워드】 endocytosis, lysosome, Neuron, SARS-CoV-2 S1, neuritic dystrophy, endolysosomal acidification, 【초록키워드】 SARS-CoV-2, Pathogenesis, COVID-19 pandemic, Brain, morphology, cross, incidence, Incubation, specimens, neurons, Hypothesis, Neurological disorder, Injury, membranes, SARS-CoV-2 S1 protein, Cell, endolysosome, tested, reported, contribute, induce, the S1 protein, released, cortical, neuronal, undetectable, with COVID-19, 【제목키워드】 Dystrophy,