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SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia (preprint)
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.12.29.424619
ABSTRACT
The emergence of SARS-CoV-2 has resulted in a global pandemic. In addition to respiratory complications as a result of SARS-CoV-2 illness, accumulating evidence suggests that neurological and neuropsychiatric symptoms are associated with the disease caused by the virus. In this study, we investigated the effects of the SARS-CoV-2 spike glycoprotein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF, IL-6, IL-1{beta} and iNOS/NO. SARS-CoV-2 spike glycoprotein S1 increased protein expressions of phospho-p65 and phospho-I{kappa}B, as well as enhancing DNA binding and transcriptional activity of NF-{kappa}B. Pro-inflammatory effects of the glycoprotein effects were reduced in the presence of BAY11-7082 (1 M). The presence of SARS-CoV-2 spike glycoprotein S1 in BV-2 microglia increased the protein expression of NLRP3, as well as caspase-1 activity. However, pre-treatment with CRID3 (1 M) or BAY11-7082 (1 M) resulted in the inhibition of NLRP3 inflammasome/caspase-1. It was also observed that CRID3 attenuated SARS-CoV-2 spike glycoprotein S1-induced increase in IL-1{beta} production. Increased protein expression of p38 MAPK was observed in BV-2 microglia stimulated with the spike glycoprotein S1, and was reduced in the presence of SKF 86002. These results have provided the first evidence demonstrating SARS-CoV-2 spike S1 glycoprotein-induced neuroinflammation in BV-2 microglia. We propose that promotion of neuroinflammation by this glycoprotein is mediated through activation of NF-{kappa}B, NLRP3 inflammasome and p38 MAPK. These results are significant because of their relevance to our understanding of neurological and neuropsychiatric symptoms observed in patients infected with SARS-CoV-2.
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Full text: Available Collection: Preprints Database: bioRxiv Main subject: Severe Acute Respiratory Syndrome / Mental Disorders Language: English Year: 2020 Document Type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Main subject: Severe Acute Respiratory Syndrome / Mental Disorders Language: English Year: 2020 Document Type: Preprint