Your browser doesn't support javascript.
Structural insight reveals SARS-CoV-2 ORF7a as an immunomodulating factor for human CD14+ monocytes.
Zhou, Ziliang; Huang, Chunliu; Zhou, Zhechong; Huang, Zhaoxia; Su, Lili; Kang, Sisi; Chen, Xiaoxue; Chen, Qiuyue; He, Suhua; Rong, Xia; Xiao, Fei; Chen, Jun; Chen, Shoudeng.
  • Zhou Z; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Huang C; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • Zhou Z; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Huang Z; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Su L; The Health Management Center, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Kang S; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Chen X; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Chen Q; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • He S; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Rong X; Institute of Clinical Transfusion, Guangzhou Blood Center, Guangzhou 510095, China.
  • Xiao F; Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
  • Chen J; Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • Chen S; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
iScience ; 24(3): 102187, 2021 Mar 19.
Article in English | MEDLINE | ID: covidwho-1093067
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 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 ß-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-1ß, 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

Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102187

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study Language: English Journal: IScience Year: 2021 Document Type: Article Affiliation country: J.isci.2021.102187