KEGG   PATHWAY: umr05160
Entry
umr05160                    Pathway                                
Name
Hepatitis C - Ursus maritimus (polar bear)
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
umr05160  Hepatitis C
umr05160

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103678713  LDLR; low-density lipoprotein receptor [KO:K12473]
103661123  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
103671059  CD81; CD81 antigen [KO:K06508]
103668088  CLDN34; claudin-34 [KO:K06087]
103660868  CLDN20; claudin-20 [KO:K06087]
103678739  CLDN18; claudin-18 isoform X2 [KO:K06087]
103660466  CLDN7; claudin-7 [KO:K06087]
103662524  CLDN25; putative claudin-25 [KO:K06087]
103657652  CLDN10; claudin-10 isoform X1 [KO:K06087]
103673231  CLDN14; claudin-14 [KO:K06087]
103673083  CLDN17; claudin-17 [KO:K06087]
103673084  CLDN8; claudin-8 [KO:K06087]
103676154  CLDN11; claudin-11 [KO:K06087]
103676021  CLDN16; LOW QUALITY PROTEIN: claudin-16 [KO:K06087]
103676022  CLDN1; claudin-1 [KO:K06087]
103679726  CLDN22; claudin-22 [KO:K06087]
103670199  CLDN15; claudin-15 isoform X1 [KO:K06087]
103668919  CLDN2; claudin-2 [KO:K06087]
103670226  CLDN3; claudin-3 [KO:K06087]
103670227  CLDN4; claudin-4 [KO:K06087]
103670827  CLDN19; claudin-19 isoform X1 [KO:K06087]
103668507  CLDN9; claudin-9 [KO:K06087]
103668508  CLDN6; claudin-6 [KO:K06087]
103658703  CLDN12; claudin-12 [KO:K06087]
121105626  CLDN23; claudin-23 [KO:K06087]
121099919  CLDN5; LOW QUALITY PROTEIN: claudin-5 [KO:K06087]
103663872  OCLN; occludin isoform X1 [KO:K06088]
103661290  2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
103661196  OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
103672422  RNASEL; LOW QUALITY PROTEIN: 2-5A-dependent ribonuclease [KO:K01165]
103667020  DDX58; antiviral innate immune response receptor RIG-I isoform X1 [KO:K12646] [EC:5.6.2.6]
103674396  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
103656774  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
103656833  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
103671004  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
103657131  IRF3; interferon regulatory factor 3 [KO:K05411]
103671092  IRF7; LOW QUALITY PROTEIN: interferon regulatory factor 7 [KO:K09447]
103662147  interferon alpha-1/2-like [KO:K05414]
103662148  interferon alpha-1/2-like [KO:K05414]
103662149  interferon alpha-2-like [KO:K05414]
103680385  interferon alpha-1/2-like [KO:K05414]
103680386  interferon alpha-1/2-like [KO:K05414]
103666985  interferon alpha-1/2-like [KO:K05414]
121103043  interferon alpha-1/2-like [KO:K05414]
103662150  IFNB1; interferon beta [KO:K05415]
103656858  IFNG; interferon gamma [KO:K04687]
103680971  TLR3; toll-like receptor 3 [KO:K05401]
103681847  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
103659308  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103664964  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
103658916  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103679680  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103679584  RELA; transcription factor p65 [KO:K04735]
103682322  TNF; tumor necrosis factor [KO:K03156]
103665330  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
103670096  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
103671577  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
103671855  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
103673470  EIF2AK4; eIF-2-alpha kinase GCN2 isoform X1 [KO:K16196] [EC:2.7.11.1]
103661943  interferon-induced protein with tetratricopeptide repeats 1 isoform X1 [KO:K14217]
103661549  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
103671936  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
103672573  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
103665967  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103673220  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
103673110  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
103663059  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
103678725  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
103659933  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
103656206  STAT2; signal transducer and activator of transcription 2 isoform X1 [KO:K11221]
103679279  IRF9; LOW QUALITY PROTEIN: interferon regulatory factor 9 [KO:K04693]
103680723  interferon-induced GTP-binding protein Mx1 isoform X1 [KO:K14754]
103680726  interferon-induced GTP-binding protein Mx2 [KO:K14754]
103658038  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
103662531  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
103657330  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X5 [KO:K03456]
103658340  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
103673291  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
103658377  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X3 [KO:K04354]
103663691  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
103659105  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
121100753  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
103679050  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
103661742  EGF; pro-epidermal growth factor isoform X2 [KO:K04357]
103674660  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103671891  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103665409  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103669173  LOW QUALITY PROTEIN: GTPase HRas-like [KO:K02833]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103665244  KRAS; GTPase KRas isoform X1 [KO:K07827]
103669422  NRAS; GTPase NRas [KO:K07828]
103669103  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103664348  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
103661509  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
103675032  YWHAQ; 14-3-3 protein theta [KO:K16197]
103669726  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
103681664  14-3-3 protein zeta/delta-like [KO:K16197]
103667175  14-3-3 protein epsilon [KO:K06630]
103681113  YWHAH; 14-3-3 protein eta [KO:K16198]
103670210  YWHAG; 14-3-3 protein gamma [KO:K16198]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103678785  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
103680384  CTNNB1; catenin beta-1 [KO:K02105]
103679423  BAD; bcl2-associated agonist of cell death [KO:K02158]
103665536  CDKN1A; cyclin-dependent kinase inhibitor 1 isoform X1 [KO:K06625]
103660368  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103682503  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
103656694  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103658796  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103677688  RB1; retinoblastoma-associated protein [KO:K06618]
103674455  E2F1; transcription factor E2F1 [KO:K17454]
103666789  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
103678383  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
103656234  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
103673673  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
103675245  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
103668115  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103661934  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
103671072  FADD; FAS-associated death domain protein [KO:K02373]
103659742  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
103680991  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
103675694  BID; BH3-interacting domain death agonist [KO:K04726]
103657107  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103665481  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
103658902  cytochrome c [KO:K08738]
103662923  cytochrome c-like [KO:K08738]
121104237  LOW QUALITY PROTEIN: cytochrome c, testis-specific-like [KO:K08738]
103660136  APAF1; LOW QUALITY PROTEIN: apoptotic protease-activating factor 1 [KO:K02084]
103666628  CASP9; caspase-9 isoform X2 [KO:K04399] [EC:3.4.22.62]
103672590  PSME3; proteasome activator complex subunit 3 [KO:K06698]
103658259  proteasome activator complex subunit 3-like [KO:K06698]
103679944  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
103674025  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
103672313  NR1H3; oxysterols receptor LXR-alpha isoform X2 [KO:K08536]
103671139  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103661697  MYC; myc proto-oncogene protein isoform X1 [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
umr03320  PPAR signaling pathway
umr04010  MAPK signaling pathway
umr04144  Endocytosis
umr04210  Apoptosis
umr04514  Cell adhesion molecules
umr04620  Toll-like receptor signaling pathway
umr04622  RIG-I-like receptor signaling pathway
umr04630  JAK-STAT signaling pathway
umr04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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