SARS-CoV-2 and SARS-CoV-2 Spike protein S1 subunit Trigger Proinflammatory Response in Macrophages in the Absence of Productive Infection

Abstract One of the hallmarks critically ill COVID-19 patients infected with SARS-CoV-2 is exaggerated inflammatory response. Though macrophages mediate responses and can produce pro-inflammatory cytokines to eliminate pathogens, infection has been shown cause immune dysfunction, leading hyperinflammation in lungs. To further understand role hyperinflammatory during infection, we a THP-1 human derived macrophage cell line SARS-CoV-2. Our results show that, though do not support viral replication, still upregulation mRNA TNFα CXCL10, which are markers COVID-related hyperinflammation. In addition, identified Spike protein S1 subunit as one factor involved macrophages. We that glycosylated, soluble upregulate CXCL10 mRNAs, well secretion TNFα, absence virus infection. Therefore, activation by may contribute lungs seen through proinflammatory such CXCL10. Supported NIH grant (R01 AI083387), Washington Research Foundation, NIGMS Predoctoral Biotechnology Training Grant 5T32GM008336