摘要：SummaryDysregulated immune cell responses have been linked to the severity of coronavirus disease 2019 (COVID-19), but the specific viral factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were currently unknown. Herein, we reveal that the Immunoglobulin-like fold ectodomain of the viral protein SARS-CoV-2 ORF7a interacts with high efficiency to CD14+monocytes in human peripheral blood, compared to pathogenic protein SARS-CoV ORF7a. The crystal structure of SARS-CoV-2 ORF7a at 2.2 Å resolution reveals three remarkable changes on the amphipathic side of the four-stranded β-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14+monocytesex vivotriggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1β, IL-8, and TNF-α. Our work demonstrates that SARS-CoV-2 ORF7a is an immunomodulating factor for immune cell binding and triggers dramatic inflammatory responses, providing promising therapeutic drug targets for pandemic COVID-19.Graphical abstractDisplay OmittedHighlights•Ig-like SARS-CoV-2 ORF7a efficiently interacts with CD14+monocytes from PBMCs•SARS-CoV-2 ORF7a structure shows distinct binding pattern to specific immune cells•SARS-CoV-2 ORF7a triggers the antigen-presenting suppression of CD14+monocytes•SARS-CoV-2 ORF7a is involved in cytokine storm propagation of patients with COVID-19Immunology; Virology
