7yp1
Cryo-EM structure of EBV gHgL-gp42 in complex with mAb 10E4 (localized refinement)
Structural highlights
FunctionGL_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 (By similarity). Publication Abstract from PubMedEpstein-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. Non-overlapping epitopes on the gHgL-gp42 complex for the rational design of a triple-antibody cocktail against EBV infection.,Hong J, Zhong L, Liu L, Wu Q, Zhang W, Chen K, Wei D, Sun H, Zhou X, Zhang X, Kang YF, Huang Y, Chen J, Wang G, Zhou Y, Chen Y, Feng QS, Yu H, Li S, Zeng MS, Zeng YX, Xu M, Zheng Q, Chen Y, Zhang X, Xia N Cell Rep Med. 2023 Nov 21;4(11):101296. doi: 10.1016/j.xcrm.2023.101296. PMID:37992686[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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