iScience
. 2021 Feb 12;102187.
doi: 10.1016/j.isci.2021.102187. Online ahead of print.
Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14 + monocytes
Ziliang Zhou 1 , Chunliu Huang 2 , Zhechong Zhou 1 , Zhaoxia Huang 1 , Lili Su 3 , Sisi Kang 1 , Xiaoxue Chen 1 , Qiuyue Chen 1 , Suhua He 1 , Xia Rong 4 , Fei Xiao 1 , Jun Chen 2 5 6 7 , Shoudeng Chen 1 8
Affiliations
- PMID: 33615195
- PMCID: PMC7879101
- DOI: 10.1016/j.isci.2021.102187
Abstract
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 Ig-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 ? 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+ monocytes ex vivo triggered 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.
Keywords: CD14+ monocyte; COVID-19; ORF7a; SARS-CoV-2; antigen-presenting function; immune cell; immunomodulating factor; proinflammatory cytokine.