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Epstein-Barr病毒gH/gL有多个病毒中和与融合抑制的脆弱部位
作者:小柯机器人 发布时间:2022/10/30 20:23:45

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。

研究人员揭示了EBV gH/gL内病毒中和和融合抑制的脆弱部位。研究人员开发了一组人类单克隆抗体(mAb),针对EBV gH/gL上五个不同的抗原位点,并防止上皮细胞和B细胞的感染。使用X射线晶体学和电子显微镜进行的结构分析显示了多个脆弱的部位,并确定了EBV gH/gL的抗原情况。在人源化小鼠EBV感染模型中,一种mAb对病毒感染和淋巴瘤提供了几乎完全的保护。这些研究结果提供了病毒融合机制的结构和抗原知识,产生了一种潜在的治疗性抗体来预防EBV疾病,并强调gH/gL是疱疹病毒疫苗和治疗的一个靶标。
 
据介绍,EBV在成年人中几乎无处不在。EBV导致传染性单核细胞增多症,并与B细胞淋巴瘤、上皮细胞恶性肿瘤和多发性硬化症有关。EBV gH/gL糖蛋白复合物促进了病毒膜与宿主细胞的融合,是中和抗体的目标。
 
附:英文原文

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

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx