KEGG   PATHWAY: dle05160
Entry
dle05160                    Pathway                                
Name
Hepatitis C - Delphinapterus leucas (beluga whale)
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
dle05160  Hepatitis C
dle05160

Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111165995  LDLR; low-density lipoprotein receptor [KO:K12473]
111187005  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
111183612  CD81; CD81 antigen [KO:K06508]
111175406  CLDN19; claudin-19 isoform X1 [KO:K06087]
111182320  CLDN3; claudin-3 [KO:K06087]
111185217  CLDN9; claudin-9 [KO:K06087]
111185219  CLDN6; claudin-6 [KO:K06087]
111166887  CLDN25; LOW QUALITY PROTEIN: putative claudin-25 [KO:K06087]
111176453  CLDN10; claudin-10 [KO:K06087]
111182000  CLDN15; claudin-15 [KO:K06087]
111173607  CLDN23; claudin-23 [KO:K06087]
111172708  CLDN1; claudin-1 [KO:K06087]
111185711  CLDN7; claudin-7 [KO:K06087]
111175517  CLDN16; claudin-16 [KO:K06087]
111167316  CLDN20; claudin-20 [KO:K06087]
111179219  CLDN18; claudin-18 isoform X1 [KO:K06087]
111175066  CLDN8; claudin-8 [KO:K06087]
111175076  CLDN17; claudin-17 [KO:K06087]
111170847  CLDN2; claudin-2 [KO:K06087]
111173597  putative claudin-24 [KO:K06087]
111182046  CLDN4; claudin-4 [KO:K06087]
111174120  CLDN11; claudin-11 [KO:K06087]
111163903  CLDN14; claudin-14 [KO:K06087]
111163047  CLDN5; claudin-5 [KO:K06087]
111180707  CLDN12; claudin-12 [KO:K06087]
111185810  OCLN; occludin isoform X1 [KO:K06088]
111162647  LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2-like [KO:K14216] [EC:2.7.7.84]
111184628  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
111184404  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
111176049  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
111173795  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
111184753  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
111180609  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
111170280  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
111171121  interferon alpha-1-like [KO:K05414]
111171122  interferon alpha-1-like isoform X1 [KO:K05414]
111163101  LOW QUALITY PROTEIN: interferon alpha-8-like [KO:K05414]
111163130  interferon alpha-1-like [KO:K05414]
111174560  IFNB1; interferon beta [KO:K05415]
111173770  IFNG; interferon gamma [KO:K04687]
111173425  TLR3; toll-like receptor 3 [KO:K05401]
111165914  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
111179772  TRAF6; TNF receptor-associated factor 6 isoform X1 [KO:K03175] [EC:2.3.2.27]
111181305  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
111172396  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111173552  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111170969  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
111173225  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
111179110  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111183745  RELA; transcription factor p65 isoform X1 [KO:K04735]
111170657  TNF; tumor necrosis factor [KO:K03156]
111187597  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
111181878  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 isoform X1 [KO:K16194] [EC:2.7.11.1]
111174878  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
111187362  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
111181760  EIF2AK4; eIF-2-alpha kinase GCN2 [KO:K16196] [EC:2.7.11.1]
111172570  LOW QUALITY PROTEIN: interferon-induced protein with tetratricopeptide repeats 1-like [KO:K14217]
111176578  LOW QUALITY PROTEIN: interferon-induced protein with tetratricopeptide repeats 1-like [KO:K14217]
111180338  EIF3E; eukaryotic translation initiation factor 3 subunit E isoform X1 [KO:K03250]
111173047  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
111166491  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
111182757  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
111163780  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
111163874  IFNAR2; interferon alpha/beta receptor 2 isoform X3 [KO:K05131]
111178461  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
111166017  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
111171663  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
111173869  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
111164116  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
111163861  LOW QUALITY PROTEIN: interferon-induced GTP-binding protein Mx1-like [KO:K14754]
111168062  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
111181079  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
111179116  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
111183056  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
111185417  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
111172180  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
111173481  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
111182447  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
111177755  PIAS1; E3 SUMO-protein ligase PIAS1 isoform X1 [KO:K04706] [EC:2.3.2.-]
111186135  EGF; pro-epidermal growth factor [KO:K04357]
111184548  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111182833  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
111174855  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
111173177  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
111170340  HRAS; GTPase HRas isoform X1 [KO:K02833]
111176851  KRAS; GTPase KRas [KO:K07827]
111179996  NRAS; GTPase NRas [KO:K07828]
111177653  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111168973  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111165554  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111180376  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
111184144  YWHAB; 14-3-3 protein beta/alpha isoform X1 [KO:K16197]
111164449  YWHAQ; 14-3-3 protein theta [KO:K16197]
111185838  YWHAE; 14-3-3 protein epsilon [KO:K06630]
111175442  14-3-3 protein gamma-like [KO:K16198]
111179149  14-3-3 protein gamma-like [KO:K16198]
111182017  YWHAG; 14-3-3 protein gamma [KO:K16198]
111162810  YWHAH; 14-3-3 protein eta [KO:K16198]
111177745  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111165994  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
111163022  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
111182181  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111166652  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111185984  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111175760  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111173839  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111179235  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111187262  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
111177559  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111176008  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111180855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111168040  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111169438  CTNNB1; catenin beta-1 [KO:K02105]
111183810  BAD; bcl2-associated agonist of cell death [KO:K02158]
111178743  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
111185755  TP53; cellular tumor antigen p53 [KO:K04451]
111173897  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
111173824  CDK4; cyclin-dependent kinase 4 isoform X1 [KO:K02089] [EC:2.7.11.22]
111180943  CDK6; cyclin-dependent kinase 6 isoform X1 [KO:K02091] [EC:2.7.11.22]
111175081  RB1; retinoblastoma-associated protein [KO:K06618]
111184273  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
111163373  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
111181407  E2F3; transcription factor E2F3 isoform X2 [KO:K06620]
111176656  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
111179654  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
111177009  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
111170265  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
111172519  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
111183629  FADD; FAS-associated death domain protein [KO:K02373]
111171726  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
111173401  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
111171724  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
111176587  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
111180640  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
111178690  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
111180543  cytochrome c [KO:K08738]
111174575  cytochrome c-like [KO:K08738]
111174031  cytochrome c-like [KO:K08738]
111172911  cytochrome c 2 [KO:K08738]
111174197  cytochrome c-like [KO:K08738]
111175930  cytochrome c-like [KO:K08738]
111187821  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
111187099  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
111166275  proteasome activator complex subunit 3-like [KO:K06698]
111166421  proteasome activator complex subunit 3 [KO:K06698]
111177070  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
111186471  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
111183967  NR1H3; oxysterols receptor LXR-alpha isoform X1 [KO:K08536]
111183632  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
111164391  MYC; myc proto-oncogene protein [KO:K04377]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C20935  2-5A
Reference
PMID:24520529
  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
PMID:23641066
  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
PMID:24509809
  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
PMID:18081727
  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
PMID:23675659
  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
PMID:23836234
  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
PMID:26586968
  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
PMID:15039538
  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
PMID:19708811
  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
PMID:20457596
  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
PMID:23836238
  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
PMID:28862649
  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
PMID:25852264
  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
PMID:16107833
  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
PMID:17467654
  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
PMID:12686421
  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
PMID:16239065
  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
PMID:15302943
  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
PMID:21250384
  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
PMID:12101418
  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
PMID:11886269
  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
PMID:15381253
  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
PMID:11514734
  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
PMID:12056797
  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
PMID:22611309
  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
PMID:17828818
  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
PMID:16611896
  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
PMID:19148799
  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
PMID:17764115
  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
PMID:18251977
  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
dle03320  PPAR signaling pathway
dle04010  MAPK signaling pathway
dle04144  Endocytosis
dle04210  Apoptosis
dle04514  Cell adhesion molecules
dle04620  Toll-like receptor signaling pathway
dle04622  RIG-I-like receptor signaling pathway
dle04630  JAK-STAT signaling pathway
dle04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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