The pathogenic role and genomic characteristics of Epstein-Barr virus in vitreoretinal lymphoma

Xiaoqing Liu; Guangjie Jiang; Chianru Tan; Kun Chen; Zhewei Sun; Jiaying Du; Bei Wang; Fuqi Ai; Yimin Ma; Yueru Tian; Yong Guo; Ming Guan

doi:10.1016/j.virs.2025.09.007

October 2025

Xiaoqing Liu, Guangjie Jiang, Chianru Tan, Kun Chen, Zhewei Sun, Jiaying Du, Bei Wang, Fuqi Ai, Yimin Ma, Yueru Tian, Yong Guo and Ming Guan. The pathogenic role and genomic characteristics of Epstein-Barr virus in vitreoretinal lymphoma[J]. Virologica Sinica, 2025, 40(5): 804-811. doi: 10.1016/j.virs.2025.09.007

Citation: Xiaoqing Liu, Guangjie Jiang, Chianru Tan, Kun Chen, Zhewei Sun, Jiaying Du, Bei Wang, Fuqi Ai, Yimin Ma, Yueru Tian, Yong Guo, Ming Guan. The pathogenic role and genomic characteristics of Epstein-Barr virus in vitreoretinal lymphoma .VIROLOGICA SINICA, 2025, 40(5) : 804-811. http://dx.doi.org/10.1016/j.virs.2025.09.007

EBV在玻璃体视网膜淋巴瘤中的致病作用及基因组特征

刘晓庆 ^a ,
蒋光洁 ^a ,
陈芊如 ^b ,
陈锟 ^a ,
孙哲伟 ^a ,
杜佳颖 ^a ,
王蓓 ^a ,
艾芙琪 ^a ,
马逸珉 ^a ,
田月如 ^a,, ,
郭永 ^b,, ,
关明 ^a,,

a 复旦大学附属华山医院检验医学科, 上海, 200040;
b. 清华大学生物医学工程学院, 北京, 100084

通讯作者： 田月如, vicky8025@126.com; 郭永, yongguo@tsinghua.edu.cn; 关明, guanming@shmu.edu.cn
收稿日期： 2025-07-22
录用日期： 2025-09-24

摘要

EBV作为一种与淋巴细胞增生性疾病和多种淋巴瘤相关的致瘤病毒，具有极高的发病率和致死率。其中，EBV阳性玻璃体视网膜淋巴瘤（VRL）极为罕见，因此，EBV在VRL中的致病作用和基因组特征尚不清楚。本研究采用数字PCR（ddPCR）结合EBV特异性免疫荧光检测了53名VRL患者玻璃体液中的EBV感染情况，发现约28%（15/53）的患者为EBV阳性。临床数据分析表明，EBV阳性VRL患者的无进展生存期（PFS）比EBV阴性患者短（P=0.004）。进一步通过EBV靶向测序和基于PCR的深度测序对VRL来源的EBV基因组特征进行了分析，发现其中5例VRL来源的EBV基因组属于同一个发育分支。此外，VRL患者来源的EBV毒株在LMP1的S229T和BPLF1的G2248R位点存在特异性突变。总之，该研究表明，EBV是导致VRL不良预后的风险因素，并首次解析了来自VRL患者玻璃体样本中的EBV序列特征全景图。这将有助于了解EBV在VRL中的致病作用，并为该疾病的诊断和治疗提供新思路。
- EB病毒
- , 玻璃体视网膜淋巴瘤
- , 基因组特征

The pathogenic role and genomic characteristics of Epstein-Barr virus in vitreoretinal lymphoma

Xiaoqing Liu ^a ,
Guangjie Jiang ^a ,
Chianru Tan ^b ,
Kun Chen ^a ,
Zhewei Sun ^a ,
Jiaying Du ^a ,
Bei Wang ^a ,
Fuqi Ai ^a ,
Yimin Ma ^a ,
Yueru Tian ^a,, ,
Yong Guo ^b,, ,
Ming Guan ^a,,

a. Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China;
b. School of Biomedical Engineering, Tsinghua University, Beijing 100084, China

Corresponding author: Yueru Tian, vicky8025@126.com Yong Guo, yongguo@tsinghua.edu.cn Ming Guan, guanming@shmu.edu.cn
Received Date: 22 July 2025
Accepted Date: 24 September 2025

Abstract

Epstein-Barr virus (EBV) infection is well-known for its association with lymphoproliferative disorders and various lymphomas, causing significant global morbidity and mortality. EBV-positive vitreoretinal lymphoma (VRL) is exceedingly rare. As a result, the pathogenic role and genomic characteristics of EBV in VRL remain poorly understood. In this study, we employed droplet digital PCR (ddPCR) combined with EBV-specific immunofluorescence assay to detect EBV in the vitreous fluid of fifty-three VRL patients. We found that approximately 28% (15/53) of the patients were EBV positive. Analysis of clinical data showed that EBV-positive VRL patients had shorter progression-free survival (PFS) compared to EBV-negative patients (P = 0.004). Additionally, through integration of EBV-targeted sequencing and PCR-based deep sequencing, we found that all five VRL-derived EBV genomes formed a distinct cluster within one phylogenetic branch. Meanwhile, several non-synonymous mutations were exclusively detected in the VRL group, including S229T in latent membrane protein 1 (LMP1) and G2248R in the Epstein-Barr virus BamHI-PraL fragment 1 (BPLF1). In conclusion, our findings suggest that EBV as a risk factor associated with poor prognosis in VRL, and we provide a genome-wide view of EBV sequence variations from VRL patients. This may offer insights into the pathogenic role of EBV in VRL and could potentially assist in the diagnosis and treatment of this disease.
- Epstein-Barr virus (EBV)
- , Vitreoretinal lymphoma (VRL)
- , Genomic variants

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