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Immune Evasion by Epstein-Barr Virus

Chapter
First Online:
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 391)

Abstract

Epstein-Bar virus (EBV) is widespread within the human population with over 90 % of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

Keywords

Immune evasion Epstein‐Barr virus Innate immunity Adaptive immunity Viral immune escape 

Abbreviations

APC

Antigen-presenting cell

ATP

Adenosine triphosphate

BART

BamHI fragment A rightward transcript

BL

Burkitt’s lymphoma

CIITA

Class II, major histocompatibility complex, transactivator

CSF-1

Colony-stimulating factor-1

E

Early

EBER

EBV-encoded RNA

EBNA

Epstein-Barr nuclear antigen

EBV

Epstein-Barr virus

ER

Endoplasmic reticulum

GPCR

G-protein-coupled receptor

HCMV

Human cytomegalovirus

HIV

Human immunodeficiency virus

HLA

Human leukocyte antigen

HSV

Herpes Simplex virus

IE

Immediate-early

IFI16

Interferon inducible protein 16

IFN

Interferon

IKK

Inhibitor of NF-κB kinase

IL

Interleukin

iNKT

Invariant natural killer T cells

IRF

Interferon-regulatory factor

ISG

Interferon-stimulated gene

JAK

Janus-kinase

KSHV

Kaposi’s sarcoma-associated herpesvirus

L

Late

LCL

Lymphoblastoid cell line

LMP

Latent membrane protein

MAPK

Mitogen-activated protein kinase

MHV68

Murine herpesvirus 68

MICB

MHC class I polypeptide-related sequence B

miRNA

MicroRNA

NF-κB

Nuclear factor-κB

NK cells

Natural killer cells

NLRP3

NLR family, pyrin domain containing 3

ORF

Open reading frame

PAMP

Pathogen-associated molecular pattern

PI3 K

Phosphatidylinositide 3-kinase

PKR

Protein kinase RNA-activated

PML-bodies

Promyelocytic leukemia bodies

PRR

Pattern-recognition receptor

qPCR

Quantitative PCR

RISC

RNA-induced silencing complex

RLR

RIG-I like receptor

shRNA

Short hairpin RNA

SOCS

Suppressor of cytokine signaling

STAT

Signal transducer and activator of transcription

TAP

Transporter associated with antigen processing

TCR

T-cell receptor

TGF

Transforming growth factor

TLR

Toll-like receptor

TNF

Tumor necrosis factor

vhs

Virion host shutoff

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Medical MicrobiologyUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of Molecular Cell BiologyLeiden University Medical CenterLeidenThe Netherlands

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