7s08 | pdb_00007s08
Crystal structure of Epstein-Barr virus gH/gL targeting antibody 770F7
Structural highlights
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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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