Crystal Structures of Bat and Human Coronavirus ORF8 Protein Ig-Like Domain Provide Insights Into the Diversity of Immune Responses

Xiaoxue Chen; Zhechong Zhou; Chunliu Huang; Ziliang Zhou; Sisi Kang; Zhaoxia Huang; Guanmin Jiang; Zhongsi Hong; Qiuyue Chen; Mei Yang; Suhua He; Siqi Liu; Jie Chen; Kenan Li; Kenan Li; Xin Li; Jing Liao; Jun Chen; Shoudeng Chen

doi:10.3389/fimmu.2021.807134

Frontiers in Immunology (Dec 2021)

Crystal Structures of Bat and Human Coronavirus ORF8 Protein Ig-Like Domain Provide Insights Into the Diversity of Immune Responses

Xiaoxue Chen,
Zhechong Zhou,
Chunliu Huang,
Ziliang Zhou,
Sisi Kang,
Zhaoxia Huang,
Guanmin Jiang,
Zhongsi Hong,
Qiuyue Chen,
Mei Yang,
Suhua He,
Siqi Liu,
Jie Chen,
Kenan Li,
Kenan Li,
Xin Li,
Jing Liao,
Jun Chen,
Shoudeng Chen

Affiliations

Xiaoxue Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Zhechong Zhou: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Chunliu Huang: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Ziliang Zhou: Department of Oral Emergency and General Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China
Sisi Kang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Zhaoxia Huang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Guanmin Jiang: Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
Zhongsi Hong: Department of Infectious Disease, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Qiuyue Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Mei Yang: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Suhua He: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Siqi Liu: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Jie Chen: Department of Gastroenterology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
Kenan Li: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Kenan Li: Department of Infectious Disease, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Xin Li: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Jing Liao: Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
Jun Chen: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
Shoudeng Chen: Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China

DOI: https://doi.org/10.3389/fimmu.2021.807134
Journal volume & issue: Vol. 12

Abstract

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ORF8 is a viral immunoglobulin-like (Ig-like) domain protein encoded by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome. It tends to evolve rapidly and interfere with immune responses. However, the structural characteristics of various coronavirus ORF8 proteins and their subsequent effects on biological functions remain unclear. Herein, we determined the crystal structures of SARS-CoV-2 ORF8 (S84) (one of the epidemic isoforms) and the bat coronavirus RaTG13 ORF8 variant at 1.62 Å and 1.76 Å resolution, respectively. Comparison of these ORF8 proteins demonstrates that the 62-77 residues in Ig-like domain of coronavirus ORF8 adopt different conformations. Combined with mutagenesis assays, the residue Cys20 of ORF8 is responsible for forming the covalent disulfide-linked dimer in crystal packing and in vitro biochemical conditions. Furthermore, immune cell-binding assays indicate that various ORF8 (SARS-CoV-2 ORF8 (L84), ORF8 (S84), and RaTG13 ORF8) proteins have different interaction capabilities with human CD14+ monocytes in human peripheral blood. These results provide new insights into the specific characteristics of various coronavirus ORF8 and suggest that ORF8 variants may influence disease-related immune responses.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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