tetano
Editor, Senior Moderator
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 [SUP]+[/SUP] monocytes
Ziliang Zhou[SUP] 1 [/SUP], Chunliu Huang[SUP] 2 [/SUP], Zhechong Zhou[SUP] 1 [/SUP], Zhaoxia Huang[SUP] 1 [/SUP], Lili Su[SUP] 3 [/SUP], Sisi Kang[SUP] 1 [/SUP], Xiaoxue Chen[SUP] 1 [/SUP], Qiuyue Chen[SUP] 1 [/SUP], Suhua He[SUP] 1 [/SUP], Xia Rong[SUP] 4 [/SUP], Fei Xiao[SUP] 1 [/SUP], Jun Chen[SUP] 2 5 6 7 [/SUP], Shoudeng Chen[SUP] 1 8 [/SUP]
Affiliations
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.
. 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 [SUP]+[/SUP] monocytes
Ziliang Zhou[SUP] 1 [/SUP], Chunliu Huang[SUP] 2 [/SUP], Zhechong Zhou[SUP] 1 [/SUP], Zhaoxia Huang[SUP] 1 [/SUP], Lili Su[SUP] 3 [/SUP], Sisi Kang[SUP] 1 [/SUP], Xiaoxue Chen[SUP] 1 [/SUP], Qiuyue Chen[SUP] 1 [/SUP], Suhua He[SUP] 1 [/SUP], Xia Rong[SUP] 4 [/SUP], Fei Xiao[SUP] 1 [/SUP], Jun Chen[SUP] 2 5 6 7 [/SUP], Shoudeng Chen[SUP] 1 8 [/SUP]
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[SUP]+[/SUP] 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[SUP]+[/SUP] 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.