Wang Hui, Zhang Ning, Xu Rongshuang, Ji Cundong, Wei Youzhen, Mi Qing
Department of Pediatrics, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.
Department of Emergency, Taian 88 Hospital, Taian, Shandong, China.
Eur J Med Res. 2025 Jun 18;30(1):486. doi: 10.1186/s40001-025-02694-1.
Epstein-Barr virus (EBV) is a gamma-herpesvirus with double-stranded DNA. Primary EBV infection leads to infectious mononucleosis (IM) in 20-50% of children and young adults. EBV establishes latent infection in B lymphocytes and can infect T lymphocytes and NK cells, potentially causing lymphoproliferative disorders (LPD) and malignancies. While the PD-1/PD-L1 pathway's role in chronic viral infections is well-established, its specific functions in EBV infection remain poorly understood. Growing evidence suggests this pathway facilitates EBV immune evasion, yet the effect of PD-1 upregulation on Epstein-Barr virus-specific CD8 + T cell function during acute IM is unclear. Furthermore, the role of PD-1/PD-L1 pathway in cytotoxic T cells and immune regulation during EBV infection is still controversial. This review systematically analyzes current knowledge on PD-1/PD-L1 signaling in EBV infection, focusing on three key aspects: (1) its dual role in maintaining immune homeostasis during acute infection while potentially facilitating viral persistence, (2) its emerging potential as a diagnostic biomarker for disease progression and prognosis, particularly during acute infectious mononucleosis, and (3) the therapeutic implications of pathway modulation. We critically evaluate recent advances that position PD-1/PD-L1 at the intersection of virology and tumor immunology, while highlighting important unanswered questions that require further investigation to optimize EBV-specific immunotherapies.
爱泼斯坦-巴尔病毒（EBV）是一种双链DNA的γ疱疹病毒。原发性EBV感染在20%至50%的儿童和年轻成年人中会导致传染性单核细胞增多症（IM）。EBV在B淋巴细胞中建立潜伏感染，并可感染T淋巴细胞和自然杀伤细胞（NK细胞），有可能导致淋巴增殖性疾病（LPD）和恶性肿瘤。虽然PD-1/PD-L1通路在慢性病毒感染中的作用已得到充分证实，但其在EBV感染中的具体功能仍知之甚少。越来越多的证据表明该通路有助于EBV免疫逃逸，但在急性IM期间PD-1上调对爱泼斯坦-巴尔病毒特异性CD8 + T细胞功能的影响尚不清楚。此外，PD-1/PD-L1通路在EBV感染期间细胞毒性T细胞和免疫调节中的作用仍存在争议。本综述系统分析了当前关于EBV感染中PD-1/PD-L1信号传导的知识，重点关注三个关键方面：（1）其在急性感染期间维持免疫稳态同时可能促进病毒持续存在的双重作用，（2）其作为疾病进展和预后的诊断生物标志物的新潜力，特别是在急性传染性单核细胞增多症期间，以及（3）通路调节的治疗意义。我们批判性地评估了将PD-1/PD-L1置于病毒学和肿瘤免疫学交叉点的最新进展，同时强调了重要的未解决问题，这些问题需要进一步研究以优化EBV特异性免疫疗法。
