Structural basis of Epstein-Barr virus gp350 receptor recognition and neutralization
Year: 2025
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: National Natural Science Foundation of China, China Postdoctoral Science Foundation, Guangdong Science and Technology Department, Science and Technology Department of Guangxi Zhuang Autonomous, Guangdong Province Introduction of Innovative R&D Team, Key Technologies Research and Development Program, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities
OpenAlex ID: W4406162378