KEGG   PATHWAY: ocu05169
Entry
ocu05169                    Pathway                                
Name
Epstein-Barr virus infection - Oryctolagus cuniculus (rabbit)
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
ocu05169  Epstein-Barr virus infection
ocu05169

Disease
H00367  Infectious mononucleosis
Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008609  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
100008616  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
100008617  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
100008733  IL6; interleukin-6 precursor [KO:K05405]
100008840  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100008856  JUN; transcription factor Jun [KO:K04448]
100008924  [KO:K07606]
100009013  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
100009036  [KO:K10151]
100009037  [KO:K06624]
100009038  [KO:K10152]
100009039  [KO:K02089] [EC:2.7.11.22]
100009040  [KO:K02091] [EC:2.7.11.22]
100009050  CALR; calreticulin precursor [KO:K08057]
100009088  TNF; tumor necrosis factor precursor [KO:K03156]
100009097  [KO:K06856]
100009292  TP53; cellular tumor antigen p53 [KO:K04451]
100009418  [KO:K10591] [EC:2.3.2.26]
100009578  TLR2; toll-like receptor 2 precursor [KO:K10159]
100101592  [KO:K04399] [EC:3.4.22.62]
100134864  [KO:K06626]
100134865  [KO:K02206] [EC:2.7.11.22]
100134866  CCNA2; cyclin-A2 [KO:K06627]
100134867  [KO:K06626]
100301546  CD44; CD44 antigen isoform X11 [KO:K06256]
100327265  MYC; myc proto-oncogene protein [KO:K04377]
100328669  PSMD4; 26S proteasome non-ATPase regulatory subunit 4 [KO:K03029]
100328685  PDIA3; protein disulfide-isomerase A3 precursor [KO:K08056] [EC:5.3.4.1]
100328905  IKBKG; NF-kappa-B essential modulator [KO:K07210]
100328929  RLA-DR-ALPHA; major histocompatibility complex, class II, DR alpha precursor [KO:K06752]
100328967  [KO:K06751]
100337822  [KO:K00922] [EC:2.7.1.153]
100337888  [KO:K03171]
100337999  [KO:K04440] [EC:2.7.11.24]
100338097  [KO:K05131]
100338269  [KO:K03035]
100338447  [KO:K03875]
100338604  [KO:K05130]
100338822  [KO:K06751]
100339067  [KO:K03037]
100339529  [KO:K06451]
100339607  [KO:K06468]
100339644  [KO:K01510] [EC:3.6.1.5]
100339821  [KO:K06751]
100339873  [KO:K04392]
100339897  [KO:K03030]
100339928  [KO:K04469]
100339953  [KO:K04432] [EC:2.7.12.2]
100340005  [KO:K09849]
100340056  [KO:K05854] [EC:2.7.10.2]
100340139  [KO:K05859] [EC:3.1.4.11]
100340530  [KO:K14216] [EC:2.7.7.84]
100340811  [KO:K04729]
100341050  [KO:K08738]
100341175  [KO:K08738]
100341358  [KO:K06752]
100341515  [KO:K08738]
100341605  [KO:K04733] [EC:2.7.11.1]
100341658  [KO:K03063]
100341695  [KO:K04441] [EC:2.7.11.24]
100342046  [KO:K14021]
100342249  [KO:K04404]
100342452  [KO:K03875]
100342664  [KO:K04440] [EC:2.7.11.24]
100342852  [KO:K04456] [EC:2.7.11.1]
100342931  [KO:K05415]
100343144  [KO:K06752]
100343190  [KO:K03175] [EC:2.3.2.27]
100343571  [KO:K04427] [EC:2.7.11.25]
100343893  [KO:K11220]
100344161  [KO:K04441] [EC:2.7.11.24]
100344432  [KO:K04693]
100344467  [KO:K11221]
100344622  [KO:K11219] [EC:2.7.10.2]
100344852  [KO:K04430] [EC:2.7.12.2]
100345181  [KO:K00922] [EC:2.7.1.153]
100345232  [KO:K03038]
100345233  [KO:K06465]
100345250  [KO:K02649]
100345380  [KO:K11644]
100345483  [KO:K16341]
100345556  [KO:K05855] [EC:2.7.10.2]
100345640  [KO:K06490]
100346379  [KO:K09389]
100346517  [KO:K06053]
100346929  [KO:K04440] [EC:2.7.11.24]
100347707  RIGI; antiviral innate immune response receptor RIG-I isoform X1 [KO:K12646] [EC:5.6.2.6]
100348082  [KO:K03028]
100348477  [KO:K04398] [EC:3.4.22.61]
100348489  [KO:K06625]
100348663  [KO:K00922] [EC:2.7.1.153]
100348778  [KO:K04692]
100348995  [KO:K06751]
100349085  [KO:K06751]
100349106  [KO:K03160]
100349155  [KO:K05653] [EC:7.4.2.14]
100349247  [KO:K06751]
100349408  [KO:K06752]
100349426  [KO:K02580]
100349667  [KO:K06752]
100349757  [KO:K06751]
100349785  [KO:K03066]
100349881  [KO:K01510] [EC:3.6.1.5]
100350168  [KO:K06752]
100350259  [KO:K11859] [EC:3.4.19.12]
100350417  [KO:K08057]
100350485  [KO:K06066]
100350591  [KO:K03062]
100350614  [KO:K04441] [EC:2.7.11.24]
100350656  RLA-DRB1; HLA class II histocompatibility antigen, DRB1 beta chain [KO:K06752]
100350679  [KO:K08055]
100350916  [KO:K03066]
100351032  [KO:K04466] [EC:2.7.11.25]
100351037  [KO:K08738]
100351163  [KO:K06752]
100351416  [KO:K06752]
100351666  [KO:K05654] [EC:7.4.2.14]
100352205  [KO:K06053]
100352218  [KO:K03511] [EC:2.7.7.7]
100352386  [KO:K10140]
100352415  RLA-DMA; histocompatibility antigen DM heterodimer heavy chain-like precursor [KO:K06752]
100352594  [KO:K11217] [EC:2.7.10.2]
100352672  [KO:K06752]
100352785  [KO:K06627]
100352809  [KO:K06452]
100352836  [KO:K03061]
100352927  [KO:K06752]
100352965  [KO:K02861] [EC:2.7.11.1]
100352996  [KO:K06856]
100353112  [KO:K12671]
100353173  [KO:K06620]
100353284  [KO:K04402]
100353328  [KO:K06856]
100353390  [KO:K05414]
100353595  [KO:K03031]
100353673  [KO:K08738]
100353706  [KO:K04456] [EC:2.7.11.1]
100353742  [KO:K04402]
100353955  [KO:K03064]
100354000  [KO:K03065]
100354213  [KO:K01510] [EC:3.6.1.5]
100354225  [KO:K07370] [EC:2.7.10.2]
100354455  [KO:K07211] [EC:2.7.11.10]
100354468  [KO:K08738]
100354611  [KO:K06751]
100354630  [KO:K03036]
100354654  [KO:K05414]
100354694  [KO:K08058]
100354716  [KO:K07371]
100354724  [KO:K08738]
100354743  [KO:K04730] [EC:2.7.11.1]
100354981  [KO:K06063]
100355084  [KO:K08738]
100355156  [KO:K06067] [EC:3.5.1.98]
100355230  [KO:K04433] [EC:2.7.12.2]
100355264  [KO:K03039]
100355340  [KO:K06452]
100355380  [KO:K06751]
100355388  [KO:K09279]
100355669  [KO:K05414]
100355675  [KO:K02159]
100355680  [KO:K03062]
100355888  [KO:K04467] [EC:2.7.11.10]
100355912  [KO:K05414]
100355948  RLA-DMB; histocompatibility antigen DM heterodimer light chain-like precursor [KO:K06752]
100355991  [KO:K04726]
100356153  [KO:K06450]
100356371  RLA-A3; MHC class I antigen-like precursor [KO:K06751]
100356401  [KO:K07209] [EC:2.7.11.10]
100356419  [KO:K05414]
100356540  [KO:K12648]
100356678  [KO:K05414]
100356863  [KO:K19202]
100356927  [KO:K05718]
100356957  [KO:K17454]
100357166  [KO:K03033]
100357194  [KO:K05414]
100357329  [KO:K08738]
100357341  [KO:K04734]
100357431  [KO:K06618]
100357708  [KO:K05414]
100357840  [KO:K08738]
100357841  [KO:K02649]
100358246  [KO:K04403]
100358389  [KO:K06627]
100358704  [KO:K06054]
100358771  [KO:K05410] [EC:2.7.11.10]
100358775  [KO:K11838] [EC:3.4.19.12]
100359054  [KO:K05872]
100359083  [KO:K03174]
100359283  [KO:K02581]
103345313  [KO:K04431] [EC:2.7.12.2]
103346035  [KO:K04441] [EC:2.7.11.24]
103346323  [KO:K09253]
103346571  [KO:K05411]
103346650  [KO:K06065]
103347220  [KO:K06856]
103347723  [KO:K08738]
103348383  [KO:K02084]
103348902  [KO:K03032]
103349397  [KO:K02161]
108175836  [KO:K08738]
108176483  [KO:K19202]
108176933  [KO:K10881]
108177422  [KO:K08738]
108178217  [KO:K04012]
108178285  [KO:K10784]
108178368  [KO:K10881]
108178670  [KO:K14216] [EC:2.7.7.84]
108178730  [KO:K08738]
127482567  [KO:K06067] [EC:3.5.1.98]
127482571  [KO:K06752]
127482739  [KO:K06065]
127483320  [KO:K08738]
127485184  [KO:K04735]
127486116  [KO:K04456] [EC:2.7.11.1]
127486194  [KO:K11218] [EC:2.7.10.2]
127487420  [KO:K02206] [EC:2.7.11.22]
127488928  [KO:K11220]
127489175  [KO:K17454]
127490241  [KO:K06691]
127491150  [KO:K11221]
Compound
C00076  Calcium cation
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
Nat Rev Cancer 4:757-68 (2004)
DOI:10.1038/nrc1452
Reference
  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
  Authors
Ning S
  Title
Innate immune modulation in EBV infection.
  Journal
Herpesviridae 2:1 (2011)
DOI:10.1186/2042-4280-2-1
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Viruses 5:1587-606 (2013)
DOI:10.3390/v5061587
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
ocu03050  Proteasome
ocu04010  MAPK signaling pathway
ocu04020  Calcium signaling pathway
ocu04064  NF-kappa B signaling pathway
ocu04110  Cell cycle
ocu04115  p53 signaling pathway
ocu04210  Apoptosis
ocu04612  Antigen processing and presentation
ocu04620  Toll-like receptor signaling pathway
ocu04622  RIG-I-like receptor signaling pathway
ocu04630  JAK-STAT signaling pathway
ocu04662  B cell receptor signaling pathway
KO pathway
ko05169   

DBGET integrated database retrieval system