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TitlePotent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.
Journal, issue, pagesCell Rep Med, Vol. 5, Issue 5, Page 101573, Year 2024
Publish dateMay 21, 2024
AuthorsGe-Xin Zhao / Xin-Yan Fang / Guo-Long Bu / Shuai-Jia-Bin Chen / Cong Sun / Ting Li / Chu Xie / Yu Wang / Shu-Xin Li / Ning Meng / Guo-Kai Feng / Qian Zhong / Xiang-Wei Kong / Zheng Liu / Mu-Sheng Zeng /
PubMed AbstractEpstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its ...Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.
External linksCell Rep Med / PubMed:38776874 / PubMed Central
MethodsEM (single particle)
Resolution3.25 Å
Structure data

37249

8khr

EMDB-37249, PDB-8khr:
Cryo-EM structure of EBV gH/gL-gp42 in complex with fab 2C1
Method: EM (single particle) / Resolution: 3.25 Å

Source
  • epstein-barr virus (strain gd1) (Epstein-Barr virus)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Human gammaherpesvirus 4 / Neutralizing antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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