Epstein-Barr-Virus and recurrent infections

Epstein-Barr virus (EBV) infects almost all humans and is usually asymptomatic, but in adolescents and young adults it can lead to infectious mononucleosis. EBV-infected B cells are mainly controlled by NK cells, iNKT cells, CD4 T cells, and CD8 T cells. Mutations in proteins important for B cell function may affect EBV infection of these cells but do not result in severe EBV infection. Some genetic disorders that affect T and NK cell function result in failure to control EBV infection but do not lead to increased susceptibility to other viral infections. These include mutations in the genes: SH2D1A, BIRC4, ITK, CD27, MAGT1, CORO1A LRBA.

EBV is the only virus that triggers proliferation of B cells. The study of these responses has helped to identify proteins that are critical for the interaction of T and/or NK cells with B cells. Mutations in three genes associated with hemophagocytic lymphohistocytosis (PRF1, STX1, STXBP2, and UNC13D) may also predispose to severe chronic active EBV disease.

Severe EBV infections may be associated with immunodeficiencies that also predispose to other viral infections and, in some cases, to other bacterial and fungal infections. These include diseases due to mutations in: PIK3CD, PIK3R1, CTPS1, STK4, GATA2, MCM4, FCGR3A, CARD11, ATM and WAS. In addition, patients with severe combined immunodeficiency, which may be due to mutations in a number of different genes, are at high risk for various infections as well as EBV B-cell lymphomas.

1. Cohen JI (2015) Primary immunodeficiencies associated with EBV disease. Curr Top Microbiol Immunol 390:241-265.