Journal
MOLECULAR NEUROBIOLOGY
Volume -, Issue -, Pages -Publisher
SPRINGER
DOI: 10.1007/s12035-023-03493-7
Keywords
ACE2; Brain; Corona virus; Cytokines; Inflammation; Microglia; Toll-like receptors; Spike protein
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SARS-CoV-2 infection leads to acute symptoms especially in the lungs known as COVID-19, primarily through the binding of its spike protein to ACE2 receptor. However, there is increasing evidence suggesting that SARS-CoV-2 infection also causes neuroinflammation, resulting in neurological, neuropsychiatric, and cognitive symptoms that persist even after the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The specific neuroimmune mechanisms involved in long-COVID have not been well characterized.
SARS-CoV-2 infects cells via its spike (S) protein binding to its surface receptor angiotensin converting enzyme 2 (ACE2) on target cells and results in acute symptoms involving especially the lungs known as COVID-19. However, increasing evidence indicates that SARS-CoV-2 infection produces neuroinflammation associated with neurological, neuropsychiatric, and cognitive symptoms persists well past the resolution of the infection, known as post-COVID-19 sequalae or long-COVID. The neuroimmune mechanism(s) involved in long-COVID have not been adequately characterized. In this study, we show that recombinant SARS-CoV-2 full-length S protein stimulates release of pro-inflammatory IL-1b, CXCL8, IL-6, and MMP-9 from cultured human microglia via TLR4 receptor activation. Instead, recombinant receptor-binding domain (RBD) stimulates release of TNF-& alpha;, IL-18, and S100B via ACE2 signaling. These results provide evidence that SARS-CoV-2 spike protein contributes to neuroinflammation through different mechanisms that may be involved in CNS pathologies associated with long-COVID.
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