Epstein–Barr Virus in Inborn Immunodeficiency—More Than Infection

SIMPLE SUMMARY: Epstein–Barr Virus (EBV) is a common virus that is readily controlled by a healthy immune system and rarely causes serious problems in infected people. However, patients with certain genetic defects of their immune system might have difficulties controlling EBV and often develop severe and life-threatening conditions, such as severe inflammation and malignancies. In this review, we provide a summary of inherited immune diseases that lead to a high susceptibility to EBV infection and discuss how this infection is associated with cancer development. ABSTRACT: Epstein–Barr Virus (EBV) is a ubiquitous virus affecting more than 90% of the world’s population. Upon infection, it establishes latency in B cells. It is a rather benign virus for immune-competent individuals, in whom infections usually go unnoticed. Nevertheless, EBV has been extensively associated with tumorigenesis. Patients suffering from certain inborn errors of immunity are at high risk of developing malignancies, while infection in the majority of immune-competent individuals does not seem to lead to immune dysregulation. Herein, we discuss how inborn mutations in TNFRSF9, CD27, CD70, CORO1A, CTPS1, ITK, MAGT1, RASGRP1, STK4, CARMIL2, SH2D1A, and XIAP affect the development, differentiation, and function of key factors involved in the immunity against EBV, leading to increased susceptibility to lymphoproliferative disease and lymphoma.