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Primary Immunodeficiencies Associated with EBV Disease

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Epstein Barr Virus Volume 1

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 390))

Abstract

Epstein-Barr virus (EBV) infects nearly all humans and usually is asymptomatic, or in the case of adolescents and young adults, it can result in infectious mononucleosis. EBV-infected B cells are controlled primarily by NK cells, iNKT cells, CD4 T cells, and CD8 T cells. While mutations in proteins important for B cell function can affect EBV infection of these cells, these mutations do not result in severe EBV infection. Some genetic disorders affecting T and NK cell function result in failure to control EBV infection, but do not result in increased susceptibility to other virus infections. These include mutations in SH2D1A, BIRC4, ITK, CD27, MAGT1, CORO1A, and LRBA. Since EBV is the only virus that induces proliferation of B cells, the study of these diseases has helped to identify proteins critical for interactions of T and/or NK cells with B cells. Mutations in three genes associated with hemophagocytic lymphohistocytosis, PRF1, STXBP2, and UNC13D, can also predispose to severe chronic active EBV disease. Severe EBV infection can be associated with immunodeficiencies that also predispose to other viral infections and in some cases 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 can be due to mutations in a number of different genes, are at high risk for various infections as well as EBV B cell lymphomas. Identification of proteins important for control of EBV may help to identify new targets for immunosuppressive therapies.

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Abbreviations

APDS:

Activated PI3Kδ syndrome

CAEBV:

Chronic active EBV disease

CARD11:

Caspase recruitment domain family, member 11

CTL:

Cytotoxic T lymphocyte

CTPS1:

Cytidine 5′-triphosphate synthase

EBV:

Epstein-Barr virus

FHL:

Familial hemophagocytic lymphohistiocytosis

GATA2:

GATA binding protein 2

HLH:

Hemophagocytic lymphohistiocytosis

HPV:

Human papillomavirus

HSCT:

Hematopoietic stem cell transplantation

iNKT:

Invariant NKT

ITK:

IL-2-inducible T cell kinase

LRBA:

LPS-responsive beige-like anchor

MagT1:

Magnesium transporter 1

MCM4:

Minichromosome maintenance complex component 4

MST1:

Mammalian sterile 20-like protein

MTOR:

Mammalian target of rapamycin

NK:

Natural killer

PASLI:

P110δ-activating mutation causing senescent T cells, lymphadenopathy, and immune deficiency

PI3K:

Phosphatidylinositol-3-OH kinase

PIP2:

Phosphatidylinositol-(4,5)-biphosphate

PIP3:

Phosphatidylinositol-(3,4,5)-triphosphate

PKC:

Protein kinase C

PLC:

Phospholipase C

PML:

Progressive multifocal leukoencephalopathy

SAP:

SLAM-associated protein

SCID:

Severe combined immunodeficiency

SH2:

Src homology 2

SM:

Sec1/munc18

SNARE:

Soluble NSF attachment protein receptor

STK4:

Serine/threonine kinase 4

XIAP:

X-linked inhibitor of apoptosis

XLP:

X-linked lymphoproliferative disease

XMEN:

X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia

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  1. Medical Virology Section, Laboratory of Infectious Diseases, National Institutes of Health, 50 South Drive, MSC 8007, Bethesda, MD, 20892, USA

    Jeffrey I. Cohen

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  1. Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland

    Christian Münz

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Cohen, J.I. (2015). Primary Immunodeficiencies Associated with EBV Disease. In: Münz, C. (eds) Epstein Barr Virus Volume 1. Current Topics in Microbiology and Immunology, vol 390. Springer, Cham. https://doi.org/10.1007/978-3-319-22822-8_10

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