近日,美国国立卫生研究院Jeffrey I. Cohen等研究人员合作发现,Epstein-Barr病毒(EBV)gH/gL有多个病毒中和与融合抑制的脆弱部位。相关论文于2022年10月27日在线发表在《免疫》杂志上。
Title: Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition
Author: Wei-Hung Chen, JungHyun Kim, Wei Bu, Nathan L. Board, Yaroslav Tsybovsky, Yanmei Wang, Anna Hostal, Sarah F. Andrews, Rebecca A. Gillespie, Misook Choe, Tyler Stephens, Eun Sung Yang, Amarendra Pegu, Caroline E. Peterson, Brian E. Fisher, John R. Mascola, Stefania Pittaluga, Adrian B. McDermott, Masaru Kanekiyo, M. Gordon Joyce, Jeffrey I. Cohen
Issue&Volume: 2022-10-27
Abstract: Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosisand is associated with B cell lymphomas, epithelial cell malignancies, and multiplesclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membranewith host cells and is a target of neutralizing antibodies. Here, we examined thesites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL.We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinctantigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structuralanalyses using X-ray crystallography and electron microscopy revealed multiple sitesof vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb providednear-complete protection against viremia and lymphoma in a humanized mouse EBV challengemodel. Our findings provide structural and antigenic knowledge of the viral fusionmachinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasizegH/gL as a target for herpesvirus vaccines and therapeutics.
DOI: 10.1016/j.immuni.2022.10.003
Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00544-1
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