KEGG   PATHWAY: ko05160
Entry
ko05160                     Pathway                                

Name
Hepatitis C
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
ko05160  Hepatitis C
ko05160

Disease
H00048  Hepatocellular carcinoma
H00413  Hepatitis C
Drug
D03501  Ciluprevir (USAN/INN)
D08876  Boceprevir (INN/USAN)
D08951  Nesbuvir (USAN)
D09012  Telaprevir (JAN/USAN/INN)
D09616  Filibuvir (USAN/INN)
D09644  Narlaprevir (USAN/INN)
D09884  Danoprevir (USAN/INN)
D09885  Danoprevir sodium (USAN)
D09971  Tegobuvir (USAN/INN)
D09987  Vaniprevir (JAN/USAN/INN)
D10065  Daclatasvir (USAN)
D10081  Simeprevir (JAN/USAN)
D10093  Asunaprevir (JAN/USAN)
D10105  Daclatasvir dihydrochloride (USAN)
D10165  Setrobuvir (USAN)
D10166  Sovaprevir (USAN)
D10366  Sofosbuvir (JAN/USAN)
D10393  Deldeprevir (USAN)
D10394  Deldeprevir sodium (USAN)
D10408  Vedroprevir (USAN)
D10425  Lomibuvir (USAN/INN)
D10442  Ledipasvir (USAN)
D10462  Faldaprevir sodium (JAN/USAN)
D10469  Simeprevir sodium (JAN)
D10553  Dasabuvir (USAN/INN)
D10554  Deleobuvir (USAN/INN)
D10576  Ombitasvir (USAN)
D10580  Paritaprevir (USAN/INN)
D10581  Dasabuvir sodium hydrate
D10597  Paritaprevir hydrate (JAN)
D10598  Ombitasvir hydrate (JAN)
D10599  Ledipasvir acetonate (JAN)
D10610  Beclabuvir (USAN/INN)
D10611  Beclabuvir hydrochloride (JAN/USAN)
D10622  Deleobuvir sodium (JAN/USAN)
D10625  Elbasvir (JAN/USAN/INN)
D10639  Grazoprevir (USAN)
D10665  Samatasvir (USAN/INN)
D10806  Velpatasvir (JAN/USAN/INN)
D10814  Glecaprevir (USAN/INN)
D10815  Glecaprevir hydrate (JAN)
D10816  Pibrentasvir (JAN/USAN/INN)
D10899  Voxilaprevir (USAN/INN)
D10996  Uprifosbuvir (USAN/INN)
D11217  Ruzasvir (USAN/INN)
D11364  Adafosbuvir (USAN)
Orthology
K12473  low-density lipoprotein receptor
K22272  HCV envelope glycoprotein E2
K13885  scavenger receptor class B, member 1
K06508  CD81 antigen
K06087  claudin
K06088  occludin
K22497  HCV non-structural protein 2
K22273  HCV serine protease NS3 [EC:3.4.21.98]
K22274  HCV non-structural protein 4A
K22498  HCV non-structural protein 4B
K22275  HCV non-structural protein 5A
K22472  HCV RNA-dependent RNA polymerase
K14216  2'-5'-oligoadenylate synthetase [EC:2.7.7.84]
K01165  ribonuclease L
K12646  ATP-dependent RNA helicase DDX58 [EC:3.6.4.13]
K12648  mitochondrial antiviral-signaling protein
K03174  TNF receptor-associated factor 3
K05410  TANK-binding kinase 1 [EC:2.7.11.10]
K07211  inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]
K05411  interferon regulatory factor 3
K09447  interferon regulatory factor 7
K05414  interferon alpha
K05415  interferon beta
K04687  interferon gamma
K05401  toll-like receptor 3
K05842  toll-like receptor adapter molecule 1
K03175  TNF receptor-associated factor 6 [EC:2.3.2.27]
K02861  receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K03156  tumor necrosis factor superfamily, member 2
K12671  C-X-C motif chemokine 10
K16194  eukaryotic translation initiation factor 2-alpha kinase 1 [EC:2.7.11.1]
K16195  eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1]
K08860  eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]
K16196  eukaryotic translation initiation factor 2-alpha kinase 4 [EC:2.7.11.1]
K22271  HCV core protein
K14217  interferon-induced protein with tetratricopeptide repeats 1
K03250  translation initiation factor 3 subunit E
K03237  translation initiation factor 2 subunit 1
K04692  signal transducer and activator of transcription 3
K04696  suppressor of cytokine signaling 3
K05130  interferon receptor 1
K05131  interferon receptor 2
K11217  Janus kinase 1 [EC:2.7.10.2]
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]
K11220  signal transducer and activator of transcription 1
K11221  signal transducer and activator of transcription 2
K04693  interferon regulatory factor 9
K14754  interferon-induced GTP-binding protein Mx
K15045  radical S-adenosyl methionine domain-containing protein 2
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]
K04706  E3 SUMO-protein ligase PIAS1 [EC:2.3.2.-]
K04357  epidermal growth factor
K04361  epidermal growth factor receptor [EC:2.7.10.1]
K04364  growth factor receptor-bound protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K16197  14-3-3 protein beta/theta/zeta
K06630  14-3-3 protein epsilon
K16198  14-3-3 protein gamma/eta
K04368  mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K04456  RAC serine/threonine-protein kinase [EC:2.7.11.1]
K03083  glycogen synthase kinase 3 beta [EC:2.7.11.26]
K02105  catenin beta 1
K02158  Bcl-2-antagonist of cell death
K06625  cyclin-dependent kinase inhibitor 1A
K04451  tumor protein p53
K02206  cyclin-dependent kinase 2 [EC:2.7.11.22]
K02089  cyclin-dependent kinase 4 [EC:2.7.11.22]
K02091  cyclin-dependent kinase 6 [EC:2.7.11.22]
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K03158  tumor necrosis factor receptor superfamily member 1A
K03171  tumor necrosis factor receptor type 1-associated DEATH domain protein
K03173  TNF receptor-associated factor 2 [EC:2.3.2.27]
K04389  tumor necrosis factor ligand superfamily member 6
K04390  tumor necrosis factor receptor superfamily member 6
K02373  FAS-associated death domain protein
K04398  caspase 8 [EC:3.4.22.61]
K02187  caspase 3 [EC:3.4.22.56]
K04724  CASP8 and FADD-like apoptosis regulator
K04726  BH3 interacting domain death agonist
K02159  apoptosis regulator BAX
K14021  Bcl-2 homologous antagonist/killer
K08738  cytochrome c
K02084  apoptotic protease-activating factor
K04399  caspase 9 [EC:3.4.22.62]
K06698  proteasome activator subunit 3 (PA28 gamma)
K08524  retinoid X receptor alpha
K07294  peroxisome proliferator-activated receptor alpha
K08536  liver X receptor alpha
K04503  G1/S-specific cyclin-D1
K04377  Myc proto-oncogene protein
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
ko03320  PPAR signaling pathway
ko04010  MAPK signaling pathway
ko04144  Endocytosis
ko04210  Apoptosis
ko04514  Cell adhesion molecules
ko04620  Toll-like receptor signaling pathway
ko04622  RIG-I-like receptor signaling pathway
ko04630  JAK-STAT signaling pathway
ko04668  TNF signaling pathway
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