Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
VA Palo Alto Health Care System, Palo Alto, CA, USA.
Nat Rev Rheumatol. 2024 Nov;20(11):729-740. doi: 10.1038/s41584-024-01167-9. Epub 2024 Oct 10.
The Epstein-Barr virus (EBV) is epidemiologically associated with development of autoimmune diseases, including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. Although there is well-established evidence for this association, the underlying mechanistic basis remains incompletely defined. In this Review, we discuss the role of EBV infection as a potentiator of autoimmune rheumatic diseases. We review the EBV life cycle, viral transcription programmes, serological profiles and lytic reactivation. We discuss the epidemiological and mechanistic associations of EBV with systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis and multiple sclerosis. We describe the potential mechanisms by which EBV might promote autoimmunity, including EBV nuclear antigen 1-mediated molecular mimicry of human autoantigens; EBV-mediated B cell reprogramming, including EBV nuclear antigen 2-mediated dysregulation of autoimmune susceptibility genes; EBV and host genetic factors, including the potential for autoimmunity-promoting strains of EBV; EBV immune evasion and insufficient host responses to control infection; lytic reactivation; and other mechanisms. Finally, we discuss the therapeutic implications and potential therapeutic approaches to targeting EBV for the treatment of autoimmune disease.
EB 病毒（EBV）与包括系统性红斑狼疮、干燥综合征、类风湿关节炎和多发性硬化症在内的自身免疫性疾病的发生在流行病学上有关联。尽管这种关联有充分的证据支持，但潜在的机制基础仍未完全明确。在这篇综述中，我们讨论了 EBV 感染作为自身免疫性风湿性疾病增强剂的作用。我们回顾了 EBV 的生命周期、病毒转录程序、血清学特征和裂解再激活。我们讨论了 EBV 与系统性红斑狼疮、干燥综合征、类风湿关节炎和多发性硬化症的流行病学和机制关联。我们描述了 EBV 可能促进自身免疫的潜在机制，包括 EBV 核抗原 1 介导的人类自身抗原的分子模拟；EBV 介导的 B 细胞重编程，包括 EBV 核抗原 2 介导的自身免疫易感性基因失调；EBV 和宿主遗传因素，包括促进自身免疫的 EBV 株；EBV 免疫逃逸和宿主对控制感染的反应不足；裂解再激活；以及其他机制。最后，我们讨论了针对 EBV 治疗自身免疫性疾病的治疗意义和潜在的治疗方法。
