KEGG   PATHWAY: ko05169Help
ko05169                     Pathway                                

Epstein-Barr virus infection
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is associated with oncogenesis. EBV infection to primary human B lymphocytes leads to induction of EBV-specific HLA-restricted cytotoxic T cells, causing infectious mononucleosis during adolescence. Primary infection with EBV is followed by latent infection in which the reservoir B cells are immortalized. EBV tumorigenic potential in Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin lymphoma, and post-transplant B cell lymphomas has been well-documented. Distinct forms of EBV latency and patterns of latent gene expression can contribute to the different tumours.
09160 Human Diseases; 09167 Infectious diseases
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Pathway map
ko05169  Epstein-Barr virus infection

Ortholog table
H00007  Hodgkin lymphoma
H00008  Burkitt lymphoma
H00054  Nasopharyngeal cancer
H00367  Infectious mononucleosis
K19450  envelope glycoprotein GP350
K19451  envelope glycoprotein H
K19452  envelope glycoprotein L
K19453  virion egress protein UL7
K04012  complement receptor type 2
K03006  DNA-directed RNA polymerase II subunit RPB1 [EC:]
K03010  DNA-directed RNA polymerase II subunit RPB2 [EC:]
K03011  DNA-directed RNA polymerase II subunit RPB3
K03008  DNA-directed RNA polymerase II subunit RPB11
K03012  DNA-directed RNA polymerase II subunit RPB4
K03015  DNA-directed RNA polymerase II subunit RPB7
K03017  DNA-directed RNA polymerase II subunit RPB9
K03013  DNA-directed RNA polymerases I, II, and III subunit RPABC1
K03014  DNA-directed RNA polymerases I, II, and III subunit RPABC2
K03016  DNA-directed RNA polymerases I, II, and III subunit RPABC3
K03009  DNA-directed RNA polymerases I, II, and III subunit RPABC4
K03007  DNA-directed RNA polymerases I, II, and III subunit RPABC5
K03018  DNA-directed RNA polymerase III subunit RPC1 [EC:]
K03021  DNA-directed RNA polymerase III subunit RPC2 [EC:]
K03027  DNA-directed RNA polymerases I and III subunit RPAC1
K03020  DNA-directed RNA polymerases I and III subunit RPAC2
K03023  DNA-directed RNA polymerase III subunit RPC3
K03026  DNA-directed RNA polymerase III subunit RPC4
K14721  DNA-directed RNA polymerase III subunit RPC5
K03025  DNA-directed RNA polymerase III subunit RPC6
K03024  DNA-directed RNA polymerase III subunit RPC7
K03022  DNA-directed RNA polymerase III subunit RPC8
K03019  DNA-directed RNA polymerase III subunit RPC11
K19454  mRNA export factor ICP27
K14290  exportin-1
K07936  GTP-binding nuclear protein Ran
K14317  nuclear pore complex protein Nup214
K06751  major histocompatibility complex, class I
K01242  ADP-ribosyl cyclase 1 [EC:]
K06477  sialophorin
K02087  cyclin-dependent kinase 1 [EC:]
K19455  serine/threonine-protein kinase BGLF4 [EC:]
K19456  Epstein-Barr nuclear antigen leader protein
K15978  A-kinase anchor protein 8-like protein
K03283  heat shock 70kDa protein 1/2/6/8
K04455  heat shock protein beta-1
K09543  heat shock protein beta-2
K16197  14-3-3 protein beta/theta/zeta
K06630  14-3-3 protein epsilon
K16198  14-3-3 protein gamma/eta
K03124  transcription initiation factor TFIIB
K15979  staphylococcal nuclease domain-containing protein 1
K03136  transcription initiation factor TFIIE subunit alpha
K03137  transcription initiation factor TFIIE subunit beta
K19457  Epstein-Barr nuclear antigen 2
K11406  histone deacetylase 4/5 [EC:]
K06063  SNW domain-containing protein 1
K06065  nuclear receptor co-repressor 2
K06053  recombining binding protein suppressor of hairless
K09438  transcription factor PU.1
K19458  Epstein-Barr nuclear antigen 6
K06067  histone deacetylase 1/2 [EC:]
K04498  E1A/CREB-binding protein [EC:]
K13784  prothymosin alpha
K19459  latent membrane protein 1
K19460  latent membrane protein 2
K06468  low affinity immunoglobulin epsilon Fc receptor
K08891  tyrosine-protein kinase Fgr [EC:]
K04377  Myc proto-oncogene protein
K04451  tumor protein p53
K03120  transcription initiation factor TFIID TATA-box-binding protein
K06625  cyclin-dependent kinase inhibitor 1A
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:]
K19461  Epstein-Barr nuclear antigen 1
K03061  26S proteasome regulatory subunit T1
K03062  26S proteasome regulatory subunit T2
K03063  26S proteasome regulatory subunit T3
K03064  26S proteasome regulatory subunit T4
K03065  26S proteasome regulatory subunit T5
K03066  26S proteasome regulatory subunit T6
K03028  26S proteasome regulatory subunit N1
K03032  26S proteasome regulatory subunit N2
K03033  26S proteasome regulatory subunit N3
K03035  26S proteasome regulatory subunit N5
K03036  26S proteasome regulatory subunit N6
K03037  26S proteasome regulatory subunit N7
K03038  26S proteasome regulatory subunit N8
K03039  26S proteasome regulatory subunit N9
K03029  26S proteasome regulatory subunit N10
K03030  26S proteasome regulatory subunit N11
K03031  26S proteasome regulatory subunit N12
K06691  26S proteasome regulatory subunit N13
K10881  26 proteasome complex subunit DSS1
K11838  ubiquitin carboxyl-terminal hydrolase 7 [EC:]
K04345  protein kinase A [EC:]
K03097  casein kinase II subunit alpha [EC:]
K03115  casein kinase II subunit beta
K19462  trans-activator protein BZLF1
K06624  cyclin-dependent kinase inhibitor 1B
K06627  cyclin-A
K02206  cyclin-dependent kinase 2 [EC:]
K06618  retinoblastoma-associated protein
K03875  F-box and leucine-rich repeat protein 1 (S-phase kinase-associated protein 2)
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04456  RAC serine/threonine-protein kinase [EC:]
K03083  glycogen synthase kinase 3 beta [EC:]
K03172  TNF receptor-associated factor 1
K03173  TNF receptor-associated factor 2 [EC:]
K03174  TNF receptor-associated factor 3
K09849  TNF receptor-associated factor 5
K04466  mitogen-activated protein kinase kinase kinase 14 [EC:]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K09253  transcription factor RelB
K04469  nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K03171  tumor necrosis factor receptor type 1-associated DEATH domain protein
K02861  receptor-interacting serine/threonine-protein kinase 1 [EC:]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K02581  NF-kappa-B inhibitor beta
K04734  NF-kappa-B inhibitor alpha
K05872  NF-kappa-B inhibitor epsilon
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04730  interleukin-1 receptor-associated kinase 1 [EC:]
K03175  TNF receptor-associated factor 6 [EC:]
K04403  TAK1-binding protein 1
K04404  TAK1-binding protein 2
K04427  mitogen-activated protein kinase kinase kinase 7 [EC:]
K04432  mitogen-activated protein kinase kinase 3 [EC:]
K04433  mitogen-activated protein kinase kinase 6 [EC:]
K04441  p38 MAP kinase [EC:]
K04430  mitogen-activated protein kinase kinase 4 [EC:]
K04431  mitogen-activated protein kinase kinase 7 [EC:]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:]
K04448  transcription factor AP-1
K04450  cyclic AMP-dependent transcription factor ATF-2
K11218  Janus kinase 3 [EC:]
K01510  apyrase [EC:]
K03160  tumor necrosis factor receptor superfamily member 5
K06256  CD44 antigen
K05718  integrin alpha L
K06492  CD58 antigen
K06490  intercellular adhesion molecule 1
K07606  vimentin
K11859  tumor necrosis factor, alpha-induced protein 3 [EC:]
K02161  apoptosis regulator Bcl-2
K06856  immunoglobulin heavy chain
K05854  tyrosine-protein kinase Lyn [EC:]
K05855  spleen tyrosine kinase [EC:]
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:]
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:]
K06465  B-lymphocyte antigen CD19
K10591  E3 ubiquitin-protein ligase NEDD4 [EC:]
K12646  ATP-dependent RNA helicase DDX58 [EC:]
K04687  interferon gamma
K05410  TANK-binding kinase 1 [EC:]
K05411  interferon regulatory factor 3
K05443  interleukin 10
K16194  eukaryotic translation initiation factor 2-alpha kinase 1 [EC:]
K16195  eukaryotic translation initiation factor 2-alpha kinase 2 [EC:]
K08860  eukaryotic translation initiation factor 2-alpha kinase 3 [EC:]
K16196  eukaryotic translation initiation factor 2-alpha kinase 4 [EC:]
K19463  apoptosis regulator BHRF1
K05134  interleukin 10 receptor alpha
K05135  interleukin 10 receptor beta
K11217  Janus kinase 1 [EC:]
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:]
K04692  signal transducer and activator of transcription 3
C00076  Calcium cation
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Kieff E, Rickinson AB.
Epstein-Barr virus and its replication.
Fields Virology. New York, Lippincott-Raven
Young LS, Rickinson AB.
Epstein-Barr virus: 40 years on.
Nat Rev Cancer 4:757-68 (2004)
Young LS, Murray PG
Epstein-Barr virus and oncogenesis: from latent genes to tumours.
Oncogene 22:5108-21 (2003)
Haan KM, Kwok WW, Longnecker R, Speck P
Epstein-Barr virus entry utilizing HLA-DP or HLA-DQ as a coreceptor.
J Virol 74:2451-4 (2000)
Knight JS, Sharma N, Robertson ES
Epstein-Barr virus latent antigen 3C can mediate the degradation of the retinoblastoma protein through an SCF cellular ubiquitin ligase.
Proc Natl Acad Sci U S A 102:18562-6 (2005)
Knight JS, Sharma N, Kalman DE, Robertson ES
A cyclin-binding motif within the amino-terminal homology domain of EBNA3C binds cyclin A and modulates cyclin A-dependent kinase activity in Epstein-Barr virus-infected cells.
J Virol 78:12857-67 (2004)
Cotter MA 2nd, Robertson ES
Modulation of histone acetyltransferase activity through interaction of epstein-barr nuclear antigen 3C with prothymosin alpha.
Mol Cell Biol 20:5722-35 (2000)
Eliopoulos AG, Caamano JH, Flavell J, Reynolds GM, Murray PG, Poyet JL, Young LS
Epstein-Barr virus-encoded latent infection membrane protein 1 regulates the processing of p100 NF-kappaB2 to p52 via an IKKgamma/NEMO-independent signalling pathway.
Oncogene 22:7557-69 (2003)
Ikeda M, Ikeda A, Longan LC, Longnecker R
The Epstein-Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases.
Virology 268:178-91 (2000)
Masucci MG
Epstein-Barr virus oncogenesis and the ubiquitin-proteasome system.
Oncogene 23:2107-15 (2004)
Luftig M, Prinarakis E, Yasui T, Tsichritzis T, Cahir-McFarland E, Inoue J, Nakano H, Mak TW, Yeh WC, Li X, Akira S, Suzuki N, Suzuki S, Mosialos G, Kieff E
Epstein-Barr virus latent membrane protein 1 activation of NF-kappaB through IRAK1 and TRAF6.
Proc Natl Acad Sci U S A 100:15595-600 (2003)
Mainou BA, Everly DN Jr, Raab-Traub N
Epstein-Barr virus latent membrane protein 1 CTAR1 mediates rodent and human fibroblast transformation through activation of PI3K.
Oncogene 24:6917-24 (2005)
Young KA, Herbert AP, Barlow PN, Holers VM, Hannan JP
Molecular basis of the interaction between complement receptor type 2 (CR2/CD21) and Epstein-Barr virus glycoprotein gp350.
J Virol 82:11217-27 (2008)
Portal D, Rosendorff A, Kieff E
Epstein-Barr nuclear antigen leader protein coactivates transcription through interaction with histone deacetylase 4.
Proc Natl Acad Sci U S A 103:19278-83 (2006)
Portal D, Zhao B, Calderwood MA, Sommermann T, Johannsen E, Kieff E
EBV nuclear antigen EBNALP dismisses transcription repressors NCoR and RBPJ from enhancers and EBNA2 increases NCoR-deficient RBPJ DNA binding.
Proc Natl Acad Sci U S A 108:7808-13 (2011)
Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD
A role for SKIP in EBNA2 activation of CBF1-repressed promoters.
J Virol 74:1939-47 (2000)
Brinkmann MM, Schulz TF
Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae.
J Gen Virol 87:1047-74 (2006)
Anderson LJ, Longnecker R
EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway.
J Gen Virol 89:1563-8 (2008)
Flemington EK, Goldfeld AE, Speck SH
Efficient transcription of the Epstein-Barr virus immediate-early BZLF1 and BRLF1 genes requires protein synthesis.
J Virol 65:7073-7 (1991)
Mauser A, Saito S, Appella E, Anderson CW, Seaman WT, Kenney S
The Epstein-Barr virus immediate-early protein BZLF1 regulates p53 function through multiple mechanisms.
J Virol 76:12503-12 (2002)
Sato Y, Shirata N, Kudoh A, Iwahori S, Nakayama S, Murata T, Isomura H, Nishiyama Y, Tsurumi T
Expression of Epstein-Barr virus BZLF1 immediate-early protein induces p53 degradation independent of MDM2, leading to repression of p53-mediated transcription.
Virology 388:204-11 (2009)
Miller CL, Burkhardt AL, Lee JH, Stealey B, Longnecker R, Bolen JB, Kieff E
Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases.
Immunity 2:155-66 (1995)
Boyle SM, Ruvolo V, Gupta AK, Swaminathan S
Association with the cellular export receptor CRM 1 mediates function and intracellular localization of Epstein-Barr virus SM protein, a regulator of gene expression.
J Virol 73:6872-81 (1999)
Callan MF, Tan L, Annels N, Ogg GS, Wilson JD, O'Callaghan CA, Steven N, McMichael AJ, Rickinson AB
Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein-Barr virus In vivo.
J Exp Med 187:1395-402 (1998)
Isobe Y.
EB virus and oncogenesis. [Japanese]
Genomu Igaku. Tokyo, Medical Review Co. Ltd.
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