Entry
Name
Epstein-Barr virus infection - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N00223 EBV EBNA1 to p53-mediated transcription
N00224 EBV EBNALP RBP-Jk-mediated transcription
N00225 EBV EBNA2 to RBP-Jk-mediated transcription
N00226 EBV EBNA3A/3B/3C to RBP-Jk-mediated transcription
N00262 EBV EBNA3C to intrinsic apoptotic pathway
N00263 EBV EBNA3C to p53-mediated transcription
N00264 EBV EBNA3C to p27-Cell cycle G1/S
N00265 EBV LMP1 to NFKB signaling pathway
N00266 EBV LMP2A to PI3K signaling pathway
N00466 EBV BPLF1 to TLR2/4-NFKB signaling pathway
N00467 EBV BPLF1 to TLR2/4-NFKB signaling pathway
N00468 EBV BPLF1 to TLR2/4-NFKB signaling pathway
N00470 EBV BGLF4 to RIG-I-like receptor signaling pathway
N00471 EBV LMP2A/2B to IFN signaling pathway
N00472 EBV LMP1 to IFN signaling pathway
N00473 EBV BGLF4 to IFN signaling pathway
N00474 EBV BHRF1 to intrinsic apoptotic pathway
N00475 EBV BHRF1 to intrinsic apoptotic pathway
N00476 EBV BHRF1 to intrinsic apoptotic pathway
N00477 EBV BHRF1 to crosstalk between extrinsic and intrinsic apoptotic pathways
N00478 EBV BARF1 to intrinsic apoptotic pathway
N00479 EBV BNLF2a to antigen processing and presentation by MHC class I molecules
N00480 EBV BILF1 to antigen processing and presentation by MHC class I molecules
N00481 EBV BZLF1 to p53-mediated transcription
N00482 EBV EBNA3C to p27-Cell cycle G1/S
N00483 EBV EBNA3C to cell cycle G1/S
N00484 EBV EBNA3C to cell cycle G1/S
N00485 EBV LMP1 to PI3K signaling pathway
N00486 EBV LMP1 to Jak-STAT signaling pathway
N00488 EBV LMP2A to BCR signaling pathway
Disease
H00367 Infectious mononucleosis
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
3108 HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752 ]
3109 HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752 ]
3111 HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752 ]
3112 HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752 ]
3113 HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752 ]
3115 HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752 ]
3117 HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752 ]
3118 HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752 ]
3119 HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752 ]
3122 HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752 ]
3123 HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752 ]
3125 HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752 ]
3126 HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752 ]
3127 HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752 ]
4615 MYD88; MYD88 innate immune signal transduction adaptor [KO:K04729 ]
10454 TAB1; TGF-beta activated kinase 1 (MAP3K7) binding protein 1 [KO:K04403 ]
23118 TAB2; TGF-beta activated kinase 1 (MAP3K7) binding protein 2 [KO:K04404 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
57506 MAVS; mitochondrial antiviral signaling protein [KO:K12648 ]
7187 TRAF3; TNF receptor associated factor 3 [KO:K03174 ]
9641 IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211 ] [EC:2.7.11.10 ]
3665 IRF7; interferon regulatory factor 7 [KO:K09447 ]
3661 IRF3; interferon regulatory factor 3 [KO:K05411 ]
3454 IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130 ]
3455 IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
5610 EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195 ] [EC:2.7.11.1 ]
3627 CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671 ]
9636 ISG15; ISG15 ubiquitin like modifier [KO:K12159 ]
355 FAS; Fas cell surface death receptor [KO:K04390 ]
8772 FADD; Fas associated via death domain [KO:K02373 ]
637 BID; BH3 interacting domain death agonist [KO:K04726 ]
596 BCL2; BCL2 apoptosis regulator [KO:K02161 ]
581 BAX; BCL2 associated X, apoptosis regulator [KO:K02159 ]
578 BAK1; BCL2 antagonist/killer 1 [KO:K14021 ]
317 APAF1; apoptotic peptidase activating factor 1 [KO:K02084 ]
916 CD3E; CD3 epsilon subunit of T-cell receptor complex [KO:K06451 ]
917 CD3G; CD3 gamma subunit of T-cell receptor complex [KO:K06452 ]
915 CD3D; CD3 delta subunit of T-cell receptor complex [KO:K06450 ]
5701 PSMC2; proteasome 26S subunit, ATPase 2 [KO:K03061 ]
5700 PSMC1; proteasome 26S subunit, ATPase 1 [KO:K03062 ]
5704 PSMC4; proteasome 26S subunit, ATPase 4 [KO:K03063 ]
5706 PSMC6; proteasome 26S subunit, ATPase 6 [KO:K03064 ]
5702 PSMC3; proteasome 26S subunit, ATPase 3 [KO:K03065 ]
5705 PSMC5; proteasome 26S subunit, ATPase 5 [KO:K03066 ]
5708 PSMD2; proteasome 26S subunit ubiquitin receptor, non-ATPase 2 [KO:K03028 ]
5707 PSMD1; proteasome 26S subunit, non-ATPase 1 [KO:K03032 ]
5709 PSMD3; proteasome 26S subunit, non-ATPase 3 [KO:K03033 ]
5718 PSMD12; proteasome 26S subunit, non-ATPase 12 [KO:K03035 ]
5717 PSMD11; proteasome 26S subunit, non-ATPase 11 [KO:K03036 ]
9861 PSMD6; proteasome 26S subunit, non-ATPase 6 [KO:K03037 ]
5713 PSMD7; proteasome 26S subunit, non-ATPase 7 [KO:K03038 ]
5719 PSMD13; proteasome 26S subunit, non-ATPase 13 [KO:K03039 ]
5710 PSMD4; proteasome 26S subunit ubiquitin receptor, non-ATPase 4 [KO:K03029 ]
10213 PSMD14; proteasome 26S subunit, non-ATPase 14 [KO:K03030 ]
5714 PSMD8; proteasome 26S subunit, non-ATPase 8 [KO:K03031 ]
11047 ADRM1; ADRM1 26S proteasome ubiquitin receptor [KO:K06691 ]
7979 SEM1; SEM1 26S proteasome subunit [KO:K10881 ]
6890 TAP1; transporter 1, ATP binding cassette subfamily B member [KO:K05653 ] [EC:7.4.2.14 ]
6891 TAP2; transporter 2, ATP binding cassette subfamily B member [KO:K05654 ] [EC:7.4.2.14 ]
3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751 ]
3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751 ]
3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751 ]
3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751 ]
3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751 ]
3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751 ]
25942 SIN3A; SIN3 transcription regulator family member A [KO:K11644 ]
9612 NCOR2; nuclear receptor corepressor 2 [KO:K06065 ]
8819 SAP30; Sin3A associated protein 30 [KO:K19202 ]
9541 CIR1; corepressor interacting with RBPJ, CIR1 [KO:K06066 ]
11317 RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053 ]
3516 RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053 ]
3280 HES1; hes family bHLH transcription factor 1 [KO:K06054 ]
864 RUNX3; RUNX family transcription factor 3 [KO:K09279 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
1647 GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402 ]
4616 GADD45B; growth arrest and DNA damage inducible beta [KO:K04402 ]
10912 GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402 ]
1643 DDB2; damage specific DNA binding protein 2 [KO:K10140 ]
7188 TRAF5; TNF receptor associated factor 5 [KO:K09849 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
5971 RELB; RELB proto-oncogene, NF-kB subunit [KO:K09253 ]
4791 NFKB2; nuclear factor kappa B subunit 2 [KO:K04469 ]
8717 TRADD; TNFRSF1A associated via death domain [KO:K03171 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
956 ENTPD3; ectonucleoside triphosphate diphosphohydrolase 3 [KO:K01510 ] [EC:3.6.1.5 ]
953 ENTPD1; ectonucleoside triphosphate diphosphohydrolase 1 [KO:K01510 ] [EC:3.6.1.5 ]
960 CD44; CD44 molecule (IN blood group) [KO:K06256 ]
3383 ICAM1; intercellular adhesion molecule 1 [KO:K06490 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
6502 SKP2; S-phase kinase associated protein 2 [KO:K03875 ]
1027 CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Young LS, Rickinson AB.
Title
Epstein-Barr virus: 40 years on.
Journal
Reference
Authors
Saha A, Robertson ES
Title
Epstein-Barr virus-associated B-cell lymphomas: pathogenesis and clinical outcomes.
Journal
Reference
Authors
Ning S
Title
Innate immune modulation in EBV infection.
Journal
Reference
Authors
Stanfield BA, Luftig MA
Title
Recent advances in understanding Epstein-Barr virus.
Journal
Reference
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
Reference
Authors
Rajsbaum R, Garcia-Sastre A
Title
Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways.
Journal
Reference
Authors
Hoffmann HH, Schneider WM, Rice CM
Title
Interferons and viruses: an evolutionary arms race of molecular interactions.
Journal
Reference
Authors
Spender LC, Inman GJ
Title
Inhibition of germinal centre apoptotic programmes by epstein-barr virus.
Journal
Reference
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
Reference
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
Reference
Authors
Melchjorsen J
Title
Learning from the messengers: innate sensing of viruses and cytokine regulation of immunity - clues for treatments and vaccines.
Journal
Reference
Authors
Hansen TH, Bouvier M
Title
MHC class I antigen presentation: learning from viral evasion strategies.
Journal
Reference
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
Reference
Authors
Horst D, Verweij MC, Davison AJ, Ressing ME, Wiertz EJ
Title
Viral evasion of T cell immunity: ancient mechanisms offering new applications.
Journal
Reference
Authors
Ghosh Roy S, Robertson ES, Saha A
Title
Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis.
Journal
Reference
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
Reference
Authors
Cai Q, Chen K, Young KH
Title
Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders.
Journal
Reference
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
Authors
Ersing I, Bernhardt K, Gewurz BE
Title
NF-kappaB and IRF7 pathway activation by Epstein-Barr virus Latent Membrane Protein 1.
Journal
Reference
Authors
Wang LW, Jiang S, Gewurz BE
Title
Epstein-Barr Virus LMP1-Mediated Oncogenicity.
Journal
Reference
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
Reference
Authors
Edwards RH, Marquitz AR, Raab-Traub N
Title
Changes in expression induced by Epstein-Barr Virus LMP1-CTAR1: potential role of bcl3.
Journal
Reference
Authors
Thorley-Lawson DA
Title
Epstein-Barr virus: exploiting the immune system.
Journal
Reference
Authors
Eliopoulos AG, Young LS
Title
LMP1 structure and signal transduction.
Journal
Reference
Authors
Holowaty MN, Sheng Y, Nguyen T, Arrowsmith C, Frappier L
Title
Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP.
Journal
Reference
Authors
Kang H, Kiess A, Chung CH
Title
Emerging biomarkers in head and neck cancer in the era of genomics.
Journal
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
Authors
Longnecker R
Title
Epstein-Barr virus latency: LMP2, a regulator or means for Epstein-Barr virus persistence?
Journal
Reference
Authors
El-Sharkawy A, Al Zaidan L, Malki A
Title
Epstein-Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in Carcinogenesis.
Journal
Reference
Authors
Dolcetti R, Masucci MG
Title
Epstein-Barr virus: induction and control of cell transformation.
Journal
Reference
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
Related pathway
hsa04612 Antigen processing and presentation
hsa04620 Toll-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04662 B cell receptor signaling pathway
KO pathway