7s07
From Proteopedia
Crystal structure of Epstein-Barr virus glycoprotein gH/gL/gp42-peptide in complex with human neutralizing antibodies 769B10 and 769C2
Structural highlights
FunctionGH_EBVB9 The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. Fusion of EBV with B-lymphocytes requires the additional receptor-binding protein gp42, which forms a complex with gH/gL. May also be required for virus attachment to epithelial cells.[1] Publication Abstract from PubMedEpstein-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. Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition.,Chen WH, Kim J, Bu W, Board NL, Tsybovsky Y, Wang Y, Hostal A, Andrews SF, Gillespie RA, Choe M, Stephens T, Yang ES, Pegu A, Peterson CE, Fisher BE, Mascola JR, Pittaluga S, McDermott AB, Kanekiyo M, Joyce MG, Cohen JI Immunity. 2022 Nov 8;55(11):2135-2148.e6. doi: 10.1016/j.immuni.2022.10.003. Epub , 2022 Oct 27. PMID:36306784[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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