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bioRxiv · 10.1101/2020.12.29.424619

SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia

Olajide, O. A.·Iwuanyanwu, V. U.·Adegbola, O. D.
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Abstract

In addition to respiratory complications produced by SARS-CoV-2, accumulating evidence suggests that some neurological symptoms are associated with the disease caused by this coronavirus. In this study, we investigated the effects of the SARS-CoV-2 spike protein 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. S1 also increased protein levels of phospho-p65 and phospho-I{kappa}B, as well as enhancing DNA binding and transcriptional activity of NF-{kappa}B. These effects of the protein were blocked in the presence of BAY11-7082 (1 M). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100 ng/mL), an action that was reduced in the presence of SKF 86002 (1 M). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1 M) and transfection with TLR4 siRNA resulted in significant reduction in TNF and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-{kappa}B and p38 MAPK, possibly as a result of TLR4 activation. These results contribute to our understanding of some of the mechanisms involved in CNS pathologies of SARS-CoV-2.

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Olajide, O. A., Iwuanyanwu, V. U., Adegbola, O. D.. 2020-12-29. SARS-CoV-2 spike glycoprotein S1 induces neuroinflammation in BV-2 microglia. https://doi.org/10.1101/2020.12.29.424619

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