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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 iScience 2021 ; 24 (3): 102187 Nephropedia Template TP
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Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14(+) monocytes #MMPMID33615195
Zhou Z; Huang C; Zhou Z; Huang Z; Su L; Kang S; Chen X; Chen Q; He S; Rong X; Xiao F; Chen J; Chen S
iScience 2021[Mar]; 24 (3): 102187 PMID33615195show ga
Dysregulated 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 A resolution reveals three remarkable changes on the amphipathic side of the four-stranded beta-sheet, implying a potential functional interface of the viral protein. Importantly, SARS-CoV-2 ORF7a coincubation with CD14(+) monocytes ex vivo triggered a decrease in HLA-DR/DP/DQ expression levels and upregulated significant production of proinflammatory cytokines, including IL-6, IL-1beta, IL-8, and TNF-alpha. 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.