Epstein–Barr virus as a potentiator of autoimmune diseases

Epstein–Barr virus as a potentiator of autoimmune diseases

William H. Robinson, Shady Younis, …Tobias V. Lanz Show authors

Nature Reviews Rheumatology (2024)Cite this article

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Abstract

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.

Key points

Epstein–Barr virus (EBV) infection is epidemiologically associated with the autoimmune rheumatic diseases systemic lupus erythematosus, Sjögren syndrome and rheumatoid arthritis, as well as other autoimmune diseases, including multiple sclerosis.

There are multiple non-exclusive mechanisms by which EBV might potentiate autoimmunity, including molecular mimicry; B cell reprogramming; genetic factors, including autoimmunity-promoting strains of EBV and host genetics; immune evasion; and lytic reactivation.

Ongoing studies are linking EBV infection and EBV reactivation with development of autoimmunity and disease activity.

Ongoing studies are defining the molecular and cellular mechanisms by which EBV might mediate autoimmune diseases.

Therapeutic targeting of EBV could provide a fundamental treatment approach for EBV-associated autoimmune diseases.

https://www.nature.com/articles/s41584-024-01167-9