7S08

Crystal structure of Epstein-Barr virus gH/gL targeting antibody 770F7

Summary for 7S08

• Entry DOI: 10.2210/pdb7s08/pdb
• Descriptor: 770F7 Fab Heavy chain, 770F7 Fab Light chain, GLYCEROL, ... (4 entities in total)
• Functional Keywords: antibody, fab, immune system, gh/gl, epstein-barr virus, herpesvirus
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 97086.35

Authors

Chen, W.-H.,Joyce, M.G. (deposition date: 2021-08-30, release date: 2022-11-09, Last modification date: 2024-11-20)

Primary citation

Chen, W.H.,Kim, J.,Bu, W.,Board, N.L.,Tsybovsky, Y.,Wang, Y.,Hostal, A.,Andrews, S.F.,Gillespie, R.A.,Choe, M.,Stephens, T.,Yang, E.S.,Pegu, A.,Peterson, C.E.,Fisher, B.E.,Mascola, J.R.,Pittaluga, S.,McDermott, A.B.,Kanekiyo, M.,Joyce, M.G.,Cohen, J.I.
Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition.
Immunity, 55:2135-2148.e6, 2022

PubMed Abstract: Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosis and is associated with B cell lymphomas, epithelial cell malignancies, and multiple sclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membrane with host cells and is a target of neutralizing antibodies. Here, we examined the sites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL. We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structural analyses using X-ray crystallography and electron microscopy revealed multiple sites of vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb provided near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model. Our findings provide structural and antigenic knowledge of the viral fusion machinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasize gH/gL as a target for herpesvirus vaccines and therapeutics.

PubMed: 36306784
DOI: 10.1016/j.immuni.2022.10.003

Experimental method

X-RAY DIFFRACTION (2.42 Å)