7YOY

Cryo-EM structure of EBV gHgL-gp42 in complex with mAbs 3E8 and 5E3 (localized refinement)

Summary for 7YOY

• Entry DOI: 10.2210/pdb7yoy/pdb
• EMDB information: 33990
• Descriptor: Soluble gp42, 5E3 heavy chain, 3E8 heavy chain, ... (5 entities in total)
• Functional Keywords: ebv, cryo-em, glycoprotein, ghgl-gp42 complex, antibody, viral protein
• Biological source: Human gammaherpesvirus 4 (Epstein-Barr virus,HHV-4,Human herpesvirus 4); More
• Total number of polymer chains: 5
• Total formula weight: 64248.65

Authors

Liu, L.,Sun, H.,Jiang, Y.,Hong, J.,Zheng, Q.,Li, S.,Chen, Y.,Xia, N. (deposition date: 2022-08-02, release date: 2024-01-31, Last modification date: 2024-11-20)

Primary citation

Hong, J.,Zhong, L.,Liu, L.,Wu, Q.,Zhang, W.,Chen, K.,Wei, D.,Sun, H.,Zhou, X.,Zhang, X.,Kang, Y.F.,Huang, Y.,Chen, J.,Wang, G.,Zhou, Y.,Chen, Y.,Feng, Q.S.,Yu, H.,Li, S.,Zeng, M.S.,Zeng, Y.X.,Xu, M.,Zheng, Q.,Chen, Y.,Zhang, X.,Xia, N.
Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection.
Cell Rep Med, 4:101296-101296, 2023

PubMed Abstract: Epstein-Barr virus (EBV) is closely associated with cancer, multiple sclerosis, and post-acute coronavirus disease 2019 (COVID-19) sequelae. There are currently no approved therapeutics or vaccines against EBV. It is noteworthy that combining multiple EBV glycoproteins can elicit potent neutralizing antibodies (nAbs) against viral infection, suggesting possible synergistic effects. Here, we characterize three nAbs (anti-gp42 5E3, anti-gHgL 6H2, and anti-gHgL 10E4) targeting different glycoproteins of the gHgL-gp42 complex. Two antibody cocktails synergistically neutralize infection in B cells (5E3+6H2+10E4) and epithelial cells (6H2+10E4) in vitro. Moreover, 5E3 alone and the 5E3+6H2+10E4 cocktail confer potent in vivo protection against lethal EBV challenge in humanized mice. The cryo-EM structure of a heptatomic gHgL-gp42 immune complex reveals non-overlapping epitopes of 5E3, 6H2, and 10E4 on the gHgL-gp42 complex. Structural and functional analyses highlight different neutralization mechanisms for each of the three nAbs. In summary, our results provide insight for the rational design of therapeutics or vaccines against EBV infection.

PubMed: 37992686
DOI: 10.1016/j.xcrm.2023.101296

Experimental method

ELECTRON MICROSCOPY (3.64 Å)