KEGG   PATHWAY: lve05160
Entry
lve05160                    Pathway                                
Name
Hepatitis C - Lipotes vexillifer (Yangtze River dolphin)
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
lve05160  Hepatitis C
lve05160

Disease
H00413  Hepatitis C
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103068617  [KO:K05414]
103068644  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103068734  NRAS; GTPase NRas [KO:K07828]
103068746  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103068842  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
103068921  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103069029  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103069117  [KO:K11220]
103069127  IFNAR2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131]
103069156  [KO:K08738]
103069181  [KO:K05414]
103069739  [KO:K05414]
103069785  APAF1; apoptotic protease-activating factor 1 isoform X1 [KO:K02084]
103069848  [KO:K14021]
103069880  IRF9; interferon regulatory factor 9 [KO:K04693]
103070103  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103070408  E2F1; transcription factor E2F1 [KO:K17454]
103070796  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
103070807  CLDN10; claudin-10 isoform X1 [KO:K06087]
103070943  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
103070944  PPP2R2C; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
103071420  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
103071645  CLDN25; LOW QUALITY PROTEIN: claudin 25 [KO:K06087]
103071774  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103071885  CLDN24; putative claudin-24 [KO:K06087]
103071962  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
103072166  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
103072426  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
103072461  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
103072682  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103073041  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
103073066  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103073219  [KO:K05414]
103073772  [KO:K05415]
103073775  CXCL10; c-X-C motif chemokine 10 [KO:K12671]
103073819  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
103073883  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
103074001  [KO:K16197]
103074371  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
103074714  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103074757  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
103074882  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103075495  [KO:K08738]
103075519  PSME3; proteasome activator complex subunit 3 isoform X1 [KO:K06698]
103075527  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103075964  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
103076043  HRAS; GTPase HRas isoform X1 [KO:K02833]
103076340  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076456  CLDN1; claudin-1 [KO:K06087]
103077054  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
103077222  IRF7; interferon regulatory factor 7 [KO:K09447]
103077417  CLDN4; claudin-4 [KO:K06087]
103077579  KRAS; GTPase KRas [KO:K07827]
103077686  CLDN3; claudin-3 [KO:K06087]
103078301  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
103078303  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103078416  CD81; CD81 antigen [KO:K06508]
103078463  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
103078468  NR1H3; oxysterols receptor LXR-alpha isoform X1 [KO:K08536]
103078531  BID; BH3-interacting domain death agonist [KO:K04726]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103078837  CLDN6; claudin-6 [KO:K06087]
103079108  CLDN9; claudin-9 [KO:K06087]
103079242  SOS1; son of sevenless homolog 1 [KO:K03099]
103079256  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
103079638  [KO:K08738]
103079766  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103079782  CLDN5; claudin-5 [KO:K06087]
103079935  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
103080036  CLDN7; claudin-7 [KO:K06087]
103080104  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
103080279  CLDN20; claudin-20 [KO:K06087]
103080339  FADD; FAS-associated death domain protein [KO:K02373]
103080409  IFIT1; interferon-induced protein with tetratricopeptide repeats 1 [KO:K14217]
103080733  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103080924  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
103081084  SOS2; son of sevenless homolog 2-like [KO:K03099]
103081090  TLR3; LOW QUALITY PROTEIN: toll-like receptor 3 [KO:K05401]
103081332  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
103081338  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103081675  CLDN19; claudin-19 isoform X1 [KO:K06087]
103081732  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
103081780  E2F2; transcription factor E2F2 [KO:K09389]
103081814  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
103081857  CLDN2; claudin-2 [KO:K06087]
103082213  [KO:K03456]
103082303  YWHAH; 14-3-3 protein eta [KO:K16198]
103082448  CLDN22; LOW QUALITY PROTEIN: claudin 22 [KO:K06087]
103082805  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
103083022  CLDN14; claudin-14 [KO:K06087]
103083032  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
103083173  [KO:K08738]
103083231  TNF; tumor necrosis factor [KO:K03156]
103083608  BAD; bcl2 antagonist of cell death [KO:K02158]
103083851  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103084066  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103084253  [KO:K16198]
103084510  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
103084536  CLDN18; claudin-18 isoform X1 [KO:K06087]
103084826  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103084836  YWHAG; LOW QUALITY PROTEIN: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma [KO:K16198]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103085220  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103085227  CLDN12; claudin-12 [KO:K06087]
103085298  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103085542  IFNG; interferon gamma [KO:K04687]
103085559  YWHAZ; 14-3-3 protein zeta/delta isoform X1 [KO:K16197]
103085746  CLDN16; claudin-16 [KO:K06087]
103085882  E2F3; transcription factor E2F3 [KO:K06620]
103086266  YWHAQ; 14-3-3 protein theta [KO:K16197]
103086495  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
103086745  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
103086967  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
103087304  RELA; transcription factor p65 isoform X1 [KO:K04735]
103087433  OAS1; 2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
103087545  MX1; LOW QUALITY PROTEIN: interferon-induced GTP-binding protein Mx1 [KO:K14754]
103087703  OAS2; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
103087818  MX2; LOW QUALITY PROTEIN: interferon-induced GTP-binding protein Mx2 [KO:K14754]
103087881  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
103087919  CLDN8; claudin-8 [KO:K06087]
103087933  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103088052  CLDN11; claudin-11 [KO:K06087]
103088190  CLDN17; claudin-17 [KO:K06087]
103088362  YWHAE; 14-3-3 protein epsilon [KO:K06630]
103088391  LDLR; low-density lipoprotein receptor [KO:K12473]
103088633  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103088738  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103088791  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
103088795  [KO:K03175] [EC:2.3.2.27]
103089123  DDX58; LOW QUALITY PROTEIN: DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 [KO:K12646] [EC:5.6.2.6]
103089138  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103089356  OCLN; occludin isoform X1 [KO:K06088]
103089875  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103089962  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103090018  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
103090271  CLDN15; claudin-15 [KO:K06087]
103090378  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
103090612  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103090661  [KO:K05414]
103090769  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103091140  CLDN23; claudin-23 [KO:K06087]
103091202  [KO:K05414]
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) 5:24 (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
lve03320  PPAR signaling pathway
lve04010  MAPK signaling pathway
lve04144  Endocytosis
lve04210  Apoptosis
lve04514  Cell adhesion molecule (CAM) interaction
lve04620  Toll-like receptor signaling pathway
lve04622  RIG-I-like receptor signaling pathway
lve04630  JAK-STAT signaling pathway
lve04668  TNF signaling pathway
KO pathway
ko05160   

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