KEGG   PATHWAY: elk05160
Entry
elk05160                    Pathway                                
Name
Hepatitis C - Enhydra lutris kenyoni (northern sea otter)
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
elk05160  Hepatitis C
elk05160

Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111162438  low-density lipoprotein receptor [KO:K12473]
111156379  scavenger receptor class B member 1 isoform X1 [KO:K13885]
111149456  CD81 antigen [KO:K06508]
111157088  claudin-34 [KO:K06087]
111151865  claudin-11 [KO:K06087]
111143502  claudin-19 [KO:K06087]
111144622  claudin-22-like [KO:K06087]
111144623  putative claudin-24 [KO:K06087]
111144642  claudin-23 [KO:K06087]
111158680  claudin-20 [KO:K06087]
111145911  claudin-4 [KO:K06087]
111147025  claudin-10 isoform X1 [KO:K06087]
111147062  LOW QUALITY PROTEIN: claudin-16 [KO:K06087]
111150697  claudin-1 isoform X1 [KO:K06087]
111161122  claudin-7 isoform X1 [KO:K06087]
111142578  claudin-5 [KO:K06087]
111155806  claudin-8 [KO:K06087]
111155821  claudin-14 [KO:K06087]
111155829  claudin-17 [KO:K06087]
111145574  claudin-15 isoform X1 [KO:K06087]
111156182  claudin-6 [KO:K06087]
111156184  LOW QUALITY PROTEIN: claudin-9 [KO:K06087]
111161308  claudin-2 [KO:K06087]
111146188  claudin-3 [KO:K06087]
111154012  putative claudin-25 [KO:K06087]
111155137  claudin-18 isoform X1 [KO:K06087]
111147329  claudin-12 [KO:K06087]
111155304  occludin [KO:K06088]
111156451  2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
111156463  2'-5'-oligoadenylate synthase 3-like isoform X1 [KO:K14216] [EC:2.7.7.84]
111156464  2'-5'-oligoadenylate synthase 2-like [KO:K14216] [EC:2.7.7.84]
111150728  2-5A-dependent ribonuclease isoform X1 [KO:K01165]
111146203  LOW QUALITY PROTEIN: probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
111141602  mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
111148495  TNF receptor-associated factor 3 isoform X1 [KO:K03174]
111142106  serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
111151174  inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
111160645  interferon regulatory factor 3 isoform X1 [KO:K05411]
111150049  interferon regulatory factor 7 [KO:K09447]
111140482  interferon alpha-1/2-like [KO:K05414]
111159856  interferon alpha-1/2-like [KO:K05414]
111159858  interferon alpha-1/2-like [KO:K05414]
111159859  interferon alpha-1/2-like [KO:K05414]
111159861  interferon alpha-1/2-like [KO:K05414]
111159862  interferon alpha-1/2-like [KO:K05414]
111156578  interferon alpha-2-like [KO:K05414]
111156593  interferon alpha-1/2-like [KO:K05414]
111156594  interferon alpha-1/2-like [KO:K05414]
111156604  interferon alpha-like [KO:K05414]
111140592  interferon alpha-1/2-like [KO:K05414]
111156606  interferon alpha-1/2-like [KO:K05414]
111156609  interferon alpha-1/2-like [KO:K05414]
111140329  interferon alpha-1/2-like [KO:K05414]
111140335  interferon alpha-1/2-like [KO:K05414]
111140336  interferon alpha-1/2-like [KO:K05414]
111156577  interferon beta [KO:K05415]
111142126  interferon gamma [KO:K04687]
111144566  toll-like receptor 3 [KO:K05401]
111161725  TIR domain-containing adapter molecule 1 [KO:K05842]
111150027  TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
111156712  receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
111144921  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111144397  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111139191  NF-kappa-B essential modulator [KO:K07210]
111140276  NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
111153611  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111149956  transcription factor p65 [KO:K04735]
111152248  tumor necrosis factor isoform X1 [KO:K03156]
111149252  C-X-C motif chemokine 10 [KO:K12671]
111145992  eukaryotic translation initiation factor 2-alpha kinase 1 isoform X1 [KO:K16194] [EC:2.7.11.1]
111158436  interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
111148064  eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
111161858  eIF-2-alpha kinase GCN2 [KO:K16196] [EC:2.7.11.1]
111145336  interferon-induced protein with tetratricopeptide repeats 1-like [KO:K14217]
111146664  eukaryotic translation initiation factor 3 subunit E [KO:K03250]
111148773  eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
111151241  signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
111160348  suppressor of cytokine signaling 3 [KO:K04696]
111155707  interferon alpha/beta receptor 1 [KO:K05130]
111155645  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
111142881  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
111162402  non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
111144592  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
111160141  signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
111140721  interferon regulatory factor 9 isoform X1 [KO:K04693]
111155708  interferon-induced GTP-binding protein Mx1 isoform X1 [KO:K14754]
111155686  interferon-induced GTP-binding protein Mx2 [KO:K14754]
111154132  radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
111153735  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
111160772  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
111144887  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
111156936  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
111149174  protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
111154409  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
111141024  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
111144543  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
111153180  E3 SUMO-protein ligase PIAS1 isoform X1 [KO:K04706] [EC:2.3.2.-]
111156359  pro-epidermal growth factor isoform X1 [KO:K04357]
111157042  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111160411  growth factor receptor-bound protein 2 [KO:K04364]
111158354  son of sevenless homolog 1 isoform X1 [KO:K03099]
111160889  son of sevenless homolog 2 isoform X1 [KO:K03099]
111140316  GTPase HRas isoform X1 [KO:K02833]
111159984  GTPase KRas isoform X1 [KO:K07827]
111143238  GTPase NRas [KO:K07828]
111151941  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
111144322  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111150582  serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
111154124  14-3-3 protein theta [KO:K16197]
111141382  14-3-3 protein beta/alpha [KO:K16197]
111146608  14-3-3 protein zeta/delta [KO:K16197]
111151387  14-3-3 protein epsilon [KO:K06630]
111160059  14-3-3 protein eta [KO:K16198]
111146124  14-3-3 protein gamma [KO:K16198]
111153158  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111161815  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111143470  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
111155224  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
111143790  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
111155003  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
111147545  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
111154641  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
111161374  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
111148765  RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111150885  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
111149921  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
111159001  catenin beta-1 [KO:K02105]
111149975  bcl2-associated agonist of cell death [KO:K02158]
111147618  cyclin-dependent kinase inhibitor 1 [KO:K06625]
111161133  cellular tumor antigen p53 [KO:K04451]
111160135  cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
111160230  cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
111147246  cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
111146911  retinoblastoma-associated protein [KO:K06618]
111141556  transcription factor E2F1 [KO:K17454]
111154729  transcription factor E2F2 isoform X1 [KO:K09389]
111138625  transcription factor E2F3 isoform X1 [KO:K06620]
111159748  tumor necrosis factor receptor superfamily member 1A [KO:K03158]
111152832  tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
111145476  TNF receptor-associated factor 2-like [KO:K03173] [EC:2.3.2.27]
111146100  TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
111150819  tumor necrosis factor ligand superfamily member 6-like [KO:K04389]
111150909  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
111144883  tumor necrosis factor receptor superfamily member 6 [KO:K04390]
111149616  FAS-associated death domain protein [KO:K02373]
111141026  caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
111144607  caspase-3 [KO:K02187] [EC:3.4.22.56]
111141134  CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
111159768  BH3-interacting domain death agonist [KO:K04726]
111160657  apoptosis regulator BAX isoform X1 [KO:K02159]
111152355  bcl-2 homologous antagonist/killer [KO:K14021]
111147305  cytochrome c isoform X1 [KO:K08738]
111142635  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
111141900  LOW QUALITY PROTEIN: uncharacterized protein LOC111141900 [KO:K08738]
111142091  apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
111154673  caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
111151137  proteasome activator complex subunit 3-like [KO:K06698]
111151323  proteasome activator complex subunit 3 isoform X1 [KO:K06698]
111146039  retinoic acid receptor RXR-alpha [KO:K08524]
111157485  peroxisome proliferator-activated receptor alpha [KO:K07294]
111150112  oxysterols receptor LXR-alpha isoform X1 [KO:K08536]
111149458  G1/S-specific cyclin-D1 [KO:K04503]
111146783  myc proto-oncogene protein [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
elk03320  PPAR signaling pathway
elk04010  MAPK signaling pathway
elk04144  Endocytosis
elk04210  Apoptosis
elk04514  Cell adhesion molecules
elk04620  Toll-like receptor signaling pathway
elk04622  RIG-I-like receptor signaling pathway
elk04630  JAK-STAT signaling pathway
elk04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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