美国国立卫生研究院Jeffrey I. Cohen等研究人员合作发现，EB病毒gp42抗体揭示受体与B细胞结合和融合的易损位点。相关论文于2024年3月12日发表在《免疫》杂志上。

研究人员表示，Epstein-Barr病毒（EBV）会导致传染性单核细胞增多症，并与B细胞淋巴瘤有关。EBV糖蛋白42（gp42）与HLA II类结合，并激活与B细胞的膜融合。

研究人员分离出了gp42特异性单克隆抗体（mAb）A10和4C12，它们利用不同的机制中和病毒感染。mAb A10在中和EBV感染和阻断与HLA II类结合方面比已知的唯一一种中和gp42的mAb F-2-1更有效；mAb 4C12在抑制糖蛋白介导的B细胞融合方面与mAb A10相似，但不阻断受体结合，而且中和感染的效果较差。gH/gL/gp42/A10和gp42/4C12复合物的晶体结构显示了gp42上受体结合和B细胞融合的两个不同的易损位点。将mAb A10被动转入人源化小鼠体内，可在EBV挑战后100%免受病毒血症和EBV淋巴瘤的侵袭。这些发现确定了EBV上的脆弱位点，可能有助于治疗和疫苗。

Title: Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells

Author: Wei Bu, Ashish Kumar, Nathan L. Board, JungHyun Kim, Kennichi Dowdell, Shu Zhang, Yona Lei, Anna Hostal, Tammy Krogmann, Yanmei Wang, Stefania Pittaluga, Joseph Marcotrigiano, Jeffrey I. Cohen

Issue&Volume: 2024/03/12

Abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with Bcell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membranefusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was morepotent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infectionand blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibitingglycoprotein-mediated B cell fusion but did not block receptor binding, and it wasless effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptorbinding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferrednearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findingsidentify vulnerable sites on EBV that may facilitate therapeutics and vaccines.

DOI: 10.1016/j.immuni.2024.02.008

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00084-0