Human genetic and immunological determinants of Epstein-Barr virus-driven disease

Antoine Gondé; Benjamin Fournier; Sylvain Latour

doi:10.1016/j.coviro.2026.101538

Human genetic and immunological determinants of Epstein-Barr virus-driven disease

Curr Opin Virol. 2026 Apr 24:76:101538. doi: 10.1016/j.coviro.2026.101538. Online ahead of print.

Authors

Antoine Gondé¹, Benjamin Fournier², Sylvain Latour³

Affiliations

¹ Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France; Imagine Institute, Paris Cité University, Paris, France.
² Imagine Institute, Paris Cité University, Paris, France; Pediatric Hematology, Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.
³ Laboratory of Lymphocyte Activation and Susceptibility to EBV, INSERM UMR 1163, Paris, France; Imagine Institute, Paris Cité University, Paris, France. Electronic address: sylvain.latour@inserm.fr.

PMID: 42034919
DOI: 10.1016/j.coviro.2026.101538

Abstract

Epstein-Barr virus (EBV) infects the vast majority of humans and establishes lifelong latency, yet causes disease in only a minority of individuals, underscoring the critical role of host determinants. This review examines the recent advances in how host genetics and immunological variation shape susceptibility to EBV across three major disease contexts. First, inborn errors of immunity have revealed essential CD8⁺ T-cell pathways governing control of EBV-driven B-cell lymphoproliferative disorders, through antigen recognition, co-stimulation, and cytokine signaling. EBV-positive T- and natural killer-cell lymphoproliferative disorders represent a second, more complex disease spectrum that arises through a multistep pathogenesis involving atypical viral entry, impaired immune control and homeostasis, and acquisition of somatic genetic alterations. Finally, we review new mechanistic evidence linking EBV to the development of autoimmune diseases, in particular multiple sclerosis and systemic lupus erythematosus, highlighting how EBV-mediated cell reprogramming amplifies immune dysregulation and self-reactivity. Together, these conditions establish EBV-associated diseases as powerful models for uncovering the complex genetic and immunological principles governing antiviral immunity and immune dysregulation.

Publication types

Review