Abstract
Epstein–Barr Virus (EBV) is a gamma-herpes virus that infects 90% of humans without any symptoms in most cases, but has an oncogenic potential, especially in immunocompromised individuals. In the past 30 years, several primary immunodeficiencies (PIDs) associated with a high risk to develop EBV-associated lymphoproliferative disorders (LPDs), essentially consisting of virus-associated hemophagocytic syndrome, non-malignant and malignant B-cell LPDs including non-Hodgkin and Hodgkin’s types of B lymphomas have been characterized. Among them are SH2D1A (SAP), XIAP, ITK, MAGT1, CD27, CD70, CTPS1, RASGRP1, and CORO1A deficiencies. Penetrance of EBV infection ranges from 50 to 100% in those PIDs. Description of large cohorts and case reports has refined the specific phenotypes associated with these PIDs helping to the diagnosis. Specific pathways required for protective immunity to EBV have emerged from studies of these PIDs. SLAM-associated protein-dependent SLAM receptors and MAGT1-dependent NKG2D pathways are important for T and NK-cell cytotoxicity toward EBV-infected B-cells, while CD27–CD70 interactions are critical to drive the expansion of EBV-specific T-cells. CTPS1 and RASGRP1 deficiencies further strengthen that T-lymphocyte expansion is a key step in the immune response to EBV. These pathways appear to be also important for the anti-tumoral immune surveillance of abnormal B cells. Monogenic PIDs should be thus considered in case of any EBV-associated LPDs.
Highlights
Specialty section: This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology
SLAM-associated protein-dependent SLAM receptors and MAGT1-dependent NKG2D pathways are important for T and NK-cell cytotoxicity toward Epstein–Barr Virus (EBV)-infected B-cells, while CD27–CD70 interactions are critical to drive the expansion of EBV-specific T-cells
EBV is an oncogenic virus known to be the causative agent of several types of neoplasms, including B, T, and NK cell lymphomas, nasopharyngeal and gastric carcinomas, and Epstein–Barr virus-associated smooth muscle tumors (EBV-SMT). 110,000–200,000 cancer cases per year are attributable to EBV worldwide [1]
Summary
MAPK pathway (ERK1/2, T-, B-cell proliferation) Actin/cytoskeleton dynamics NK cytotoxicity (Continued). Additional findings in mice indicated that this inhibitory effect was independent of FynT, but depends of the blocking activity of SAP, and leads to decreased conjugate formation between CD8+ T or NK cells and SLAMF-expressing target cells like B cells [50, 51]. In this context, other activation pathways of cytotoxicity such as NKG2D may not compensate for the defective function of 2B4 and SLAMF6. NK-cell and CD8+ T-cell cytotoxicity toward other APCs or target cells than B cells including non-hematopoietic
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