Structural basis of Epstein-Barr virus gp350 receptor recognition and neutralization

Cong Sun; Xin-Yan Fang; Guo-Long Bu; Lan-Yi Zhong; Chu Xie; Ge-Xin Zhao; Sen-Fang Sui; Zheng Liu; Mu-Sheng Zeng

doi:10.1016/j.celrep.2024.115168

Structural basis of Epstein-Barr virus gp350 receptor recognition and neutralization

Cell Rep. 2025 Jan 8;44(1):115168. doi: 10.1016/j.celrep.2024.115168. Online ahead of print.

Authors

Cong Sun¹, Xin-Yan Fang², Guo-Long Bu³, Lan-Yi Zhong³, Chu Xie³, Ge-Xin Zhao³, Sen-Fang Sui², Zheng Liu⁴, Mu-Sheng Zeng⁵

Affiliations

¹ State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: [email protected].
² Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
³ State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
⁴ Cryo-electron Microscopy Center, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China. Electronic address: [email protected].
⁵ State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. Electronic address: [email protected].

PMID: 39792550
DOI: 10.1016/j.celrep.2024.115168

Abstract

Epstein-Barr virus (EBV) is an oncogenic virus associated with multiple lymphoid malignancies and autoimmune diseases. During infection in B cells, EBV uses its major glycoprotein gp350 to recognize the host receptor CR2, initiating viral attachment, a process that has lacked direct structural evidence for decades. In this study, we resolved the structure of the gp350-CR2 complex, elucidated their key interactions, and determined the site-specific N-glycosylation map of gp350. Our findings reveal that CR2 primarily binds to gp350 through an electrostatically complementary and glycan-free interface and that the diversity of key residues in CR2 across different species influences EBV host selectivity mediated by gp350. With the confirmed binding, we constructed a CR2-Fc antibody analog that targets the vulnerable site of gp350, demonstrating a potent neutralization effect against EBV infection in B cells. Our work provides essential structural insights into the mechanism of EBV infection and host tropism, suggesting a potential antiviral agent.

Keywords: CP: Microbiology; CP: Molecular biology; EBV; complement receptor 2; glycoprotein; neutralization; structure.