KEGG   PATHWAY: ocu05160
Entry
ocu05160                    Pathway                                
Name
Hepatitis C - Oryctolagus cuniculus (rabbit)
Description
Hepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the cytoplasm of the host cell and forms membrane-associated replication complexes along with non-structural proteins. Viral RNA can trigger the RIG-I pathway and interferon production during this process. Translated HCV protein products regulate immune response to inhibit the action of interferon. HCV core and NS5A proteins appear to be the most important molecules with regulatory functions that modulate transcription, cellular proliferation, and apoptosis.
Class
Human Diseases; Infectious disease: viral
Pathway map
ocu05160  Hepatitis C
ocu05160

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100009086  LDLR; low density lipoprotein receptor [KO:K12473]
100009590  SCARB1; scavenger receptor class B member 1 [KO:K13885]
100350530  CLDN23; claudin 23 [KO:K06087]
100346496  CLDN14; claudin 14 [KO:K06087]
108175450  CLDN34; claudin 34 [KO:K06087]
100340963  CLDN4; claudin 4 [KO:K06087]
100341220  CLDN3; claudin 3 [KO:K06087]
100337855  CLDN9; claudin 9 [KO:K06087]
100342165  CLDN6; claudin 6 [KO:K06087]
100357702  CLDN15; claudin 15 [KO:K06087]
100354623  CLDN17; claudin 17 [KO:K06087]
100354880  CLDN8; claudin 8 [KO:K06087]
100353209  CLDN2; claudin 2 [KO:K06087]
100356567  CLDN20; claudin 20 [KO:K06087]
100340730  CLDN22; claudin 22 [KO:K06087]
100352273  CLDN11; claudin 11 [KO:K06087]
100037713  CLDN1; claudin 1 [KO:K06087]
100357396  CLDN19; claudin 19 [KO:K06087]
100349260  CLDN18; claudin 18 [KO:K06087]
100356384  CLDN16; claudin 16 [KO:K06087]
100338591  CLDN7; claudin 7 [KO:K06087]
100351218  CLDN5; claudin 5 [KO:K06087]
100341067  CLDN25; claudin 25 [KO:K06087]
100355124  CLDN10; claudin 10 [KO:K06087]
108175401  putative claudin-24 [KO:K06087]
100338492  OCLN; occludin [KO:K06088]
100340530  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
100340787  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
108178670  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
100343787  RNASEL; ribonuclease L [KO:K01165]
100347707  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:3.6.4.13]
100356540  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
100359083  TRAF3; TNF receptor associated factor 3 [KO:K03174]
100358771  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
100354455  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
103346571  IRF3; interferon regulatory factor 3 [KO:K05411]
100358763  IRF7; interferon regulatory factor 7 [KO:K09447]
100353390  interferon alpha-21-like [KO:K05414]
100355669  interferon alpha-21-like [KO:K05414]
100355912  interferon alpha-5-like [KO:K05414]
100357708  interferon alpha-21-like [KO:K05414]
100354654  interferon alpha-21-like [KO:K05414]
100356419  interferon alpha-14-like [KO:K05414]
100357194  interferon alpha-21-like [KO:K05414]
100356678  interferon alpha-1/13-like [KO:K05414]
100342931  IFNB1; interferon beta 1 [KO:K05415]
100008602  IFNG; interferon gamma [KO:K04687]
100009024  TLR3; toll like receptor 3 [KO:K05401]
100343190  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
100352965  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
100355888  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100356401  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100328905  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100357341  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100349426  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100009088  TNF; tumor necrosis factor [KO:K03156]
100353112  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
100009522  EIF2AK1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
100009013  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
100354847  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
100358284  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
100342826  interferon-induced protein with tetratricopeptide repeats 1-like [KO:K14217]
100342069  IFIT1B; interferon-induced protein with tetratricopeptide repeats 1B [KO:K14217]
100346441  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
100339093  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
100348778  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
100338604  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
100338097  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
100352594  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
100344622  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
100343893  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
100344467  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
100344432  IRF9; interferon regulatory factor 9 [KO:K04693]
100008606  interferon-induced GTP-binding protein Mx2 [KO:K14754]
100359014  MX1; MX dynamin like GTPase 1 [KO:K14754]
100009451  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
100347276  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
100355092  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
100355758  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
100328617  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
100009139  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
100328616  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
100348286  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
100009252  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
100009300  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
100339509  PIAS1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
100008808  EGF; epidermal growth factor [KO:K04357]
100008806  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100342500  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100356615  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
100346391  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
100347487  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
100344241  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100351964  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
100347407  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100340437  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
100358299  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
100008930  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100342694  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
100358813  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
100328734  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
100354276  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
100009316  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100347345  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100348561  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100357841  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100345250  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100348663  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
100345181  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100337822  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100342852  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100353706  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100348842  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100125985  CTNNB1; catenin beta 1 [KO:K02105]
100358587  BAD; BCL2 associated agonist of cell death [KO:K02158]
100348489  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
100009292  TP53; tumor protein p53 [KO:K04451]
100134865  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
100009039  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
100009040  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
100357431  RB1; RB transcriptional corepressor 1 [KO:K06618]
100356957  E2F1; E2F transcription factor 1 [KO:K17454]
100346379  E2F2; E2F transcription factor 2 [KO:K09389]
100353173  E2F3; E2F transcription factor 3 [KO:K06620]
100346106  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
100337888  TRADD; TNFRSF1A associated via death domain [KO:K03171]
100344073  FASLG; Fas ligand [KO:K04389]
100008609  FAS; Fas cell surface death receptor [KO:K04390]
103346753  FADD; Fas associated via death domain [KO:K02373]
100348477  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
100008840  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
100346964  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
100355991  BID; BH3 interacting domain death agonist [KO:K04726]
100355675  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
100342046  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
100357840  cytochrome c-like [KO:K08738]
100355084  cytochrome c [KO:K08738]
100341050  cytochrome c-like [KO:K08738]
100354468  cytochrome c-like [KO:K08738]
100357329  cytochrome c [KO:K08738]
100341515  cytochrome c-like [KO:K08738]
100353673  cytochrome c, testis-specific [KO:K08738]
100351037  cytochrome c-like [KO:K08738]
100341175  cytochrome c [KO:K08738]
103347723  cytochrome c-like [KO:K08738]
100354724  cytochrome c-like [KO:K08738]
103351673  cytochrome c-like [KO:K08738]
108178730  cytochrome c-like [KO:K08738]
108177422  cytochrome c-like [KO:K08738]
103348383  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
100101592  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
100352610  PSME3; proteasome activator subunit 3 [KO:K06698]
100356422  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
100352900  NR1H3; nuclear receptor subfamily 1 group H member 3 [KO:K08536]
100327265  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C20935  2-5A
Reference
  Authors
Hassan M, Selimovic D, El-Khattouti A, Ghozlan H, Haikel Y, Abdelkader O
  Title
Hepatitis C virus-host interactions: Etiopathogenesis and therapeutic strategies.
  Journal
World J Exp Med 2:7-25 (2012)
DOI:10.5493/wjem.v2.i2.7
Reference
  Authors
Yamauchi Y, Helenius A
  Title
Virus entry at a glance.
  Journal
J Cell Sci 126:1289-95 (2013)
DOI:10.1242/jcs.119685
Reference
  Authors
Feneant L, Levy S, Cocquerel L
  Title
CD81 and hepatitis C virus (HCV) infection.
  Journal
Viruses 6:535-72 (2014)
DOI:10.3390/v6020535
Reference
  Authors
Dubuisson J, Helle F, Cocquerel L
  Title
Early steps of the hepatitis C virus life cycle.
  Journal
Cell Microbiol 10:821-7 (2008)
DOI:10.1111/j.1462-5822.2007.01107.x
Reference
  Authors
Liang TJ, Ghany MG
  Title
Current and future therapies for hepatitis C virus infection.
  Journal
N Engl J Med 368:1907-17 (2013)
DOI:10.1056/NEJMra1213651
Reference
  Authors
Scheel TK, Rice CM
  Title
Understanding the hepatitis C virus life cycle paves the way for highly effective therapies.
  Journal
Nat Med 19:837-49 (2013)
DOI:10.1038/nm.3248
Reference
  Authors
Holmes JA, Thompson AJ
  Title
Interferon-free combination therapies for the treatment of hepatitis C: current insights.
  Journal
Hepat Med 7:51-70 (2015)
DOI:10.2147/HMER.S55864
Reference
  Authors
Taguchi T, Nagano-Fujii M, Akutsu M, Kadoya H, Ohgimoto S, Ishido S, Hotta H
  Title
Hepatitis C virus NS5A protein interacts with 2',5'-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner.
  Journal
J Gen Virol 85:959-69 (2004)
DOI:10.1099/vir.0.19513-0
Reference
  Authors
Horner SM, Gale M Jr
  Title
Intracellular innate immune cascades and interferon defenses that control hepatitis C virus.
  Journal
J Interferon Cytokine Res 29:489-98 (2009)
DOI:10.1089/jir.2009.0063
Reference
  Authors
Lemon SM
  Title
Induction and evasion of innate antiviral responses by hepatitis C virus.
  Journal
J Biol Chem 285:22741-7 (2010)
DOI:10.1074/jbc.R109.099556
Reference
  Authors
Horner SM, Gale M Jr
  Title
Regulation of hepatic innate immunity by hepatitis C virus.
  Journal
Nat Med 19:879-88 (2013)
DOI:10.1038/nm.3253
Reference
  Authors
Ortega-Prieto AM, Dorner M
  Title
Immune Evasion Strategies during Chronic Hepatitis B and C Virus Infection.
  Journal
Vaccines (Basel) 5:E24 (2017)
DOI:10.3390/vaccines5030024
Reference
  Authors
Yang DR, Zhu HZ
  Title
Hepatitis C virus and antiviral innate immunity: who wins at tug-of-war?
  Journal
World J Gastroenterol 21:3786-800 (2015)
DOI:10.3748/wjg.v21.i13.3786
Reference
  Authors
Gale M Jr, Foy EM
  Title
Evasion of intracellular host defence by hepatitis C virus.
  Journal
Nature 436:939-45 (2005)
DOI:10.1038/nature04078
Reference
  Authors
Bode JG, Brenndorfer ED, Haussinger D
  Title
Subversion of innate host antiviral strategies by the hepatitis C virus.
  Journal
Arch Biochem Biophys 462:254-65 (2007)
DOI:10.1016/j.abb.2007.03.033
Reference
  Authors
Panteva M, Korkaya H, Jameel S
  Title
Hepatitis viruses and the MAPK pathway: is this a survival strategy?
  Journal
Virus Res 92:131-40 (2003)
DOI:10.1016/S0168-1702(02)00356-8
Reference
  Authors
Pang R, Tse E, Poon RT
  Title
Molecular pathways in hepatocellular carcinoma.
  Journal
Cancer Lett 240:157-69 (2006)
DOI:10.1016/j.canlet.2005.08.031
Reference
  Authors
Macdonald A, Harris M
  Title
Hepatitis C virus NS5A: tales of a promiscuous protein.
  Journal
J Gen Virol 85:2485-502 (2004)
DOI:10.1099/vir.0.80204-0
Reference
  Authors
He Y, Staschke KA, Tan SL
  Title
HCV NS5A: A Multifunctional Regulator of Cellular Pathways and Virus Replication
  Journal
Hepatitis C Viruses: Genomes and Molecular Biology (2006)
Reference
  Authors
Lan KH, Sheu ML, Hwang SJ, Yen SH, Chen SY, Wu JC, Wang YJ, Kato N, Omata M, Chang FY, Lee SD
  Title
HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis.
  Journal
Oncogene 21:4801-11 (2002)
DOI:10.1038/sj.onc.1205589
Reference
  Authors
Majumder M, Ghosh AK, Steele R, Zhou XY, Phillips NJ, Ray R, Ray RB
  Title
Hepatitis C virus NS5A protein impairs TNF-mediated hepatic apoptosis, but not by an anti-FAS antibody, in transgenic mice.
  Journal
Virology 294:94-105 (2002)
DOI:10.1006/viro.2001.1309
Reference
  Authors
Hassan M, Ghozlan H, Abdel-Kader O
  Title
Activation of RB/E2F signaling pathway is required for the modulation of hepatitis C virus core protein-induced cell growth in liver and non-liver cells.
  Journal
Cell Signal 16:1375-85 (2004)
DOI:10.1016/j.cellsig.2004.04.005
Reference
  Authors
Kwun HJ, Jung EY, Ahn JY, Lee MN, Jang KL
  Title
p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3.
  Journal
J Gen Virol 82:2235-41 (2001)
DOI:10.1099/0022-1317-82-9-2235
Reference
  Authors
Yamanaka T, Uchida M, Doi T
  Title
Innate form of HCV core protein plays an important role in the localization and the function of HCV core protein.
  Journal
Biochem Biophys Res Commun 294:521-7 (2002)
DOI:10.1016/S0006-291X(02)00507-7
Reference
  Authors
Lim EJ, Chin R, Angus PW, Torresi J
  Title
Enhanced apoptosis in post-liver transplant hepatitis C: effects of virus and immunosuppressants.
  Journal
World J Gastroenterol 18:2172-9 (2012)
DOI:10.3748/wjg.v18.i18.2172
Reference
  Authors
Fischer R, Baumert T, Blum HE
  Title
Hepatitis C virus infection and apoptosis.
  Journal
World J Gastroenterol 13:4865-72 (2007)
DOI:10.3748/wjg.v13.i36.4865
Reference
  Authors
Saito K, Meyer K, Warner R, Basu A, Ray RB, Ray R
  Title
Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated apoptosis by a protective effect involving cellular FLICE inhibitory protein.
  Journal
J Virol 80:4372-9 (2006)
DOI:10.1128/JVI.80.9.4372-4379.2006
Reference
  Authors
Koike K
  Title
Steatosis, liver injury, and hepatocarcinogenesis in hepatitis C viral infection.
  Journal
J Gastroenterol 44 Suppl 19:82-8 (2009)
DOI:10.1007/s00535-008-2276-4
Reference
  Authors
Tanaka N, Moriya K, Kiyosawa K, Koike K, Aoyama T
  Title
Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: implications for HCV-associated hepatocarcinogenesis.
  Journal
Int J Cancer 122:124-31 (2008)
DOI:10.1002/ijc.23056
Reference
  Authors
Tan A, Yeh SH, Liu CJ, Cheung C, Chen PJ
  Title
Viral hepatocarcinogenesis: from infection to cancer.
  Journal
Liver Int 28:175-88 (2008)
DOI:10.1111/j.1478-3231.2007.01652.x
Related
pathway
ocu03320  PPAR signaling pathway
ocu04010  MAPK signaling pathway
ocu04144  Endocytosis
ocu04210  Apoptosis
ocu04514  Cell adhesion molecules
ocu04620  Toll-like receptor signaling pathway
ocu04622  RIG-I-like receptor signaling pathway
ocu04630  JAK-STAT signaling pathway
ocu04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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