KEGG PATHWAY: map05169

PATHWAY: map05169

Entry

map05169                    Pathway

Name

Epstein-Barr virus infection

Description

Epstein-Barr virus (EBV) is a gamma-herpes virus that widely infects human populations predominantly at an early age but remains mostly asymptomatic. EBV has been linked to a wide spectrum of human malignancies, including nasopharyngeal carcinoma and other hematologic cancers, like Hodgkin's lymphoma, Burkitt's lymphoma (BL), B-cell immunoblastic lymphoma in HIV patients, and posttransplant-associated lymphoproliferative diseases. EBV has the unique ability to establish life-long latent infection in primary human B lymphocytes. During latent infection, EBV expresses a small subset of genes, including 6 nuclear antigens (EBNA-1, -2, -3A, -3B, -3C, and -LP), 3 latent membrane proteins (LMP-1, -2A, and -2B), 2 small noncoding RNAs (EBER-1 and 2). On the basis of these latent gene expression, three different latency patterns associated with the types of cancers are recognized.

Class

Human Diseases; Infectious disease: viral

Pathway map

map05169

Epstein-Barr virus infection

Disease

H00367

Infectious mononucleosis

Reference

PMID:15510157

Authors

Young LS, Rickinson AB.

Title

Epstein-Barr virus: 40 years on.

Journal

Nat Rev Cancer 4:757-68 (2004)
DOI:10.1038/nrc1452

Reference

PMID:21372216

Authors

Saha A, Robertson ES

Title

Epstein-Barr virus-associated B-cell lymphomas: pathogenesis and clinical outcomes.

Journal

Clin Cancer Res 17:3056-63 (2011)
DOI:10.1158/1078-0432.CCR-10-2578

Reference

PMID:21429244

Authors

Ning S

Title

Innate immune modulation in EBV infection.

Journal

Herpesviridae 2:1 (2011)
DOI:10.1186/2042-4280-2-1

Reference

PMID:28408983

Authors

Stanfield BA, Luftig MA

Title

Recent advances in understanding Epstein-Barr virus.

Journal

F1000Res 6:386 (2017)
DOI:10.12688/f1000research.10591.1

Reference

PMID:24586164

Authors

van Gent M, Braem SG, de Jong A, Delagic N, Peeters JG, Boer IG, Moynagh PN, Kremmer E, Wiertz EJ, Ovaa H, Griffin BD, Ressing ME

Title

Epstein-Barr virus large tegument protein BPLF1 contributes to innate immune evasion through interference with toll-like receptor signaling.

Journal

PLoS Pathog 10:e1003960 (2014)
DOI:10.1371/journal.ppat.1003960

Reference

PMID:23850008

Authors

Rajsbaum R, Garcia-Sastre A

Title

Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways.

Journal

Trends Microbiol 21:421-9 (2013)
DOI:10.1016/j.tim.2013.06.006

Reference

PMID:25704559

Authors

Hoffmann HH, Schneider WM, Rice CM

Title

Interferons and viruses: an evolutionary arms race of molecular interactions.

Journal

Trends Immunol 36:124-38 (2015)
DOI:10.1016/j.it.2015.01.004

Reference

PMID:22110506

Authors

Spender LC, Inman GJ

Title

Inhibition of germinal centre apoptotic programmes by epstein-barr virus.

Journal

Adv Hematol 2011:829525 (2011)
DOI:10.1155/2011/829525

Reference

PMID:23303627

Authors

Fu Q, He C, Mao ZR

Title

Epstein-Barr virus interactions with the Bcl-2 protein family and apoptosis in human tumor cells.

Journal

J Zhejiang Univ Sci B 14:8-24 (2013)
DOI:10.1631/jzus.B1200189

Reference

PMID:29116588

Authors

Wang Y, Banerjee S, Ding L, Cai C, Wei F, Cai Q

Title

The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers.

Journal

Virol Sin 32:357-368 (2017)
DOI:10.1007/s12250-017-4081-9

Reference

PMID:23435233

Authors

Melchjorsen J

Title

Learning from the messengers: innate sensing of viruses and cytokine regulation of immunity - clues for treatments and vaccines.

Journal

Viruses 5:470-527 (2013)
DOI:10.3390/v5020470

Reference

PMID:19498380

Authors

Hansen TH, Bouvier M

Title

MHC class I antigen presentation: learning from viral evasion strategies.

Journal

Nat Rev Immunol 9:503-13 (2009)
DOI:10.1038/nri2575

Reference

PMID:18977445

Authors

Ressing ME, Horst D, Griffin BD, Tellam J, Zuo J, Khanna R, Rowe M, Wiertz EJ

Title

Epstein-Barr virus evasion of CD8(+) and CD4(+) T cell immunity via concerted actions of multiple gene products.

Journal

Semin Cancer Biol 18:397-408 (2008)
DOI:10.1016/j.semcancer.2008.10.008

Reference

PMID:21146386

Authors

Horst D, Verweij MC, Davison AJ, Ressing ME, Wiertz EJ

Title

Viral evasion of T cell immunity: ancient mechanisms offering new applications.

Journal

Curr Opin Immunol 23:96-103 (2011)
DOI:10.1016/j.coi.2010.11.005

Reference

PMID:27886133

Authors

Ghosh Roy S, Robertson ES, Saha A

Title

Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis.

Journal

Biomolecules 6:E46 (2016)
DOI:10.3390/biom6040046

Reference

PMID:22249143

Authors

Dawson CW, Port RJ, Young LS

Title

The role of the EBV-encoded latent membrane proteins LMP1 and LMP2 in the pathogenesis of nasopharyngeal carcinoma (NPC).

Journal

Semin Cancer Biol 22:144-53 (2012)
DOI:10.1016/j.semcancer.2012.01.004

Reference

PMID:25613730

Authors

Cai Q, Chen K, Young KH

Title

Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders.

Journal

Exp Mol Med 47:e133 (2015)
DOI:10.1038/emm.2014.105

Reference

PMID:17601372

Authors

Zheng H, Li LL, Hu DS, Deng XY, Cao Y

Title

Role of Epstein-Barr virus encoded latent membrane protein 1 in the carcinogenesis of nasopharyngeal carcinoma.

Journal

Cell Mol Immunol 4:185-96 (2007)

Reference

PMID:23793113

Authors

Ersing I, Bernhardt K, Gewurz BE

Title

NF-kappaB and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1.

Journal

Viruses 5:1587-606 (2013)
DOI:10.3390/v5061587

Reference

PMID:28835489

Authors

Wang LW, Jiang S, Gewurz BE

Title

Epstein-Barr Virus LMP1-Mediated Oncogenicity.

Journal

J Virol 91:e01718-16 (2017)
DOI:10.1128/JVI.01718-16

Reference

PMID:12740915

Authors

Mori N, Morishita M, Tsukazaki T, Yamamoto N

Title

Repression of Smad-dependent transforming growth factor-beta signaling by Epstein-Barr virus latent membrane protein 1 through nuclear factor-kappaB.

Journal

Int J Cancer 105:661-8 (2003)
DOI:10.1002/ijc.11146

Reference

PMID:25873381

Authors

Edwards RH, Marquitz AR, Raab-Traub N

Title

Changes in expression induced by Epstein-Barr Virus LMP1-CTAR1: potential role of bcl3.

Journal

MBio 6:e00441-15 (2015)
DOI:10.1128/mBio.00441-15

Reference

PMID:11905817

Authors

Thorley-Lawson DA

Title

Epstein-Barr virus: exploiting the immune system.

Journal

Nat Rev Immunol 1:75-82 (2001)
DOI:10.1038/35095584

Reference

PMID:11669605

Authors

Eliopoulos AG, Young LS

Title

LMP1 structure and signal transduction.

Journal

Semin Cancer Biol 11:435-44 (2001)
DOI:10.1006/scbi.2001.0410

Reference

PMID:14506283

Authors

Holowaty MN, Sheng Y, Nguyen T, Arrowsmith C, Frappier L

Title

Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP.

Journal

J Biol Chem 278:47753-61 (2003)
DOI:10.1074/jbc.M307200200

Reference

PMID:25403939

Authors

Kang H, Kiess A, Chung CH

Title

Emerging biomarkers in head and neck cancer in the era of genomics.

Journal

Nat Rev Clin Oncol 12:11-26 (2015)
DOI:10.1038/nrclinonc.2014.192

Reference

PMID:29932446

Authors

Tornesello ML, Annunziata C, Tornesello AL, Buonaguro L, Buonaguro FM

Title

Human Oncoviruses and p53 Tumor Suppressor Pathway Deregulation at the Origin of Human Cancers.

Journal

Cancers (Basel) 10:E213 (2018)
DOI:10.3390/cancers10070213

Reference

PMID:19649319

Authors

Sato Y, Kamura T, Shirata N, Murata T, Kudoh A, Iwahori S, Nakayama S, Isomura H, Nishiyama Y, Tsurumi T

Title

Degradation of phosphorylated p53 by viral protein-ECS E3 ligase complex.

Journal

PLoS Pathog 5:e1000530 (2009)
DOI:10.1371/journal.ppat.1000530

Reference

PMID:19244339

Authors

Saha A, Murakami M, Kumar P, Bajaj B, Sims K, Robertson ES

Title

Epstein-Barr virus nuclear antigen 3C augments Mdm2-mediated p53 ubiquitination and degradation by deubiquitinating Mdm2.

Journal

J Virol 83:4652-69 (2009)
DOI:10.1128/JVI.02408-08

Reference

PMID:19394062

Authors

Yi F, Saha A, Murakami M, Kumar P, Knight JS, Cai Q, Choudhuri T, Robertson ES

Title

Epstein-Barr virus nuclear antigen 3C targets p53 and modulates its transcriptional and apoptotic activities.

Journal

Virology 388:236-47 (2009)
DOI:10.1016/j.virol.2009.03.027

Reference

PMID:25635182

Authors

Kumar P, Murakami M, Kaul R, Saha A, Cai Q, Robertson ES

Title

Deregulation of the cell cycle machinery by Epstein-Barr virus nuclear antigen 3C.

Journal

Future Virol 4:79-91 (2009)
DOI:10.2217/17460794.4.1.79

Reference

PMID:10818681

Authors

Longnecker R

Title

Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence?

Journal

Adv Cancer Res 79:175-200 (2000)
DOI:10.1016/s0065-230x(00)79006-3

Reference

PMID:30116721

Authors

El-Sharkawy A, Al Zaidan L, Malki A

Title

Epstein-Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in Carcinogenesis.

Journal

Front Oncol 8:265 (2018)
DOI:10.3389/fonc.2018.00265

Reference

PMID:12811813

Authors

Dolcetti R, Masucci MG

Title

Epstein-Barr virus: induction and control of cell transformation.

Journal

J Cell Physiol 196:207-18 (2003)
DOI:10.1002/jcp.10263

Reference

PMID:21347341

Authors

Saha A, Halder S, Upadhyay SK, Lu J, Kumar P, Murakami M, Cai Q, Robertson ES

Title

Epstein-Barr virus nuclear antigen 3C facilitates G1-S transition by stabilizing and enhancing the function of cyclin D1.

Journal

PLoS Pathog 7:e1001275 (2011)
DOI:10.1371/journal.ppat.1001275

Related
pathway

map03050

Proteasome

map04010

MAPK signaling pathway

map04020

Calcium signaling pathway

map04064

NF-kappa B signaling pathway

map04110

Cell cycle

map04115

p53 signaling pathway

map04210

Apoptosis

map04612

Antigen processing and presentation

map04620

Toll-like receptor signaling pathway

map04622

RIG-I-like receptor signaling pathway

map04630

JAK-STAT signaling pathway

map04662

B cell receptor signaling pathway

KO pathway

ko05169

All links

Chemical substance (3)   
   KEGG COMPOUND (3)   
Gene (596426)   
   KEGG ORTHOLOGY (172)   
   RefGene (596254)   
Literature (35)   
   PubMed (35)   
All databases (596464)   

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