近日，中山大学教授曾木圣及其小组报道，R9AP是上皮细胞和B细胞中EBV感染的常见受体。2025年6月18日，国际知名学术期刊《自然》发表了这一成果。

课题组人员确定R9AP是EBV进入上皮细胞和B细胞的关键受体。R9AP沉默或敲除后，R9AP衍生肽和R9AP单克隆抗体均显著抑制EBV进入两种细胞类型，而R9AP过表达则促进EBV进入两种细胞类型。R9AP直接与EBV糖蛋白gH/gL复合物结合，启动gH/gL–gB介导的膜离子。值得注意的是，R9AP与gH/gL的相互作用被高度竞争的gH/gL中和抗体AMMO1抑制，该抗体阻断EBV上皮细胞和B细胞的进入。

此外，R9AP在B细胞或上皮细胞中分别与EBV gp42-人白细胞抗原II类或gH/ gL-EPHA2复合物协同介导病毒和细胞膜离子。该研究团队认为R9AP是B细胞和上皮细胞的重要共同受体，也是EBV的潜在预防和疫苗靶点。

据介绍，EB病毒（EBV）持续感染超过90%的人群，引起单核细胞增多症、自身免疫性疾病易感性和上皮细胞或B细胞来源的多种恶性肿瘤。EBV通过病毒糖蛋白与不同宿主受体的相互作用感染上皮细胞和B细胞，但目前尚不清楚是否有一种共同的受体介导其两种主要宿主细胞靶点的感染。

附：英文原文

Title: R9AP is a common receptor for EBV infection in epithelial cells and B cells

Author: Li, Yan, Zhang, Hua, Sun, Cong, Dong, Xiao-Dong, Xie, Chu, Liu, Yuan-Tao, Lin, Ruo-Bin, Kong, Xiang-Wei, Hu, Zhu-Long, Ma, Xiao-Yan, Dai, Dan-Ling, Zhu, Qian-Ying, Li, Yu-Chun, Li, Ying, Liu, Shang-Xin, Yuan, Li, Zhou, Peng-Hui, Gao, Song, Tang, Ya-Ping, Yang, Jin-Ying, Han, Ping, McGuire, Andrew T., Zhao, Bo, Bei, Jin-Xin, Robertson, Erle, Zeng, Yi-Xin, Zhong, Qian, Zeng, Mu-Sheng

Issue&Volume: 2025-06-18

Abstract: Epstein–Barr virus (EBV) persistently infects more than 90% of the human population, causing infectious mononucleosis1, susceptibility to autoimmune diseases2 and multiple malignancies of epithelial or B cell-origin3. EBV infects epithelial cells and B cells through interaction between viral glycoproteins and different host receptors4, but it has remained unknown whether a common receptor mediates infection of its two major host cell targets. Here, we establish R9AP as a crucial EBV receptor for entry into epithelial and B cells. R9AP silencing or knockout, R9AP-derived peptide and R9AP monoclonal antibody each significantly inhibit, whereas R9AP overexpression promotes, EBV uptake into both cell types. R9AP binds directly to the EBV glycoprotein gH/gL complex to initiate gH/gL–gB-mediated membrane fusion. Notably, the interaction of R9AP with gH/gL is inhibited by the highly competitive gH/gL-neutralizing antibody AMMO1, which blocks EBV epithelial and B cell entry. Moreover, R9AP mediates viral and cellular membrane fusion in cooperation with EBV gp42–human leukocyte antigen class II or gH/gL–EPHA2 complexes in B cells or epithelial cells, respectively. We propose R9AP as the crucial common receptor of B cells and epithelial cells and a potential prophylactic and vaccine target for EBV.

DOI: 10.1038/s41586-025-09166-w

Source: https://www.nature.com/articles/s41586-025-09166-w