KEGG   PATHWAY: tup05160
Entry
tup05160                    Pathway                                
Name
Hepatitis C - Tupaia chinensis (Chinese tree shrew)
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
tup05160  Hepatitis C
tup05160

Disease
H00413  Hepatitis C
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102468327  CLDN19; claudin 19 [KO:K06087]
102468736  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
102468740  PIAS1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
102468854  [KO:K08738]
102469395  CLDN2; claudin 2 [KO:K06087]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469574  [KO:K05414]
102469861  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
102470174  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102470277  RXRA; retinoid X receptor alpha [KO:K08524]
102470542  IFNG; interferon gamma [KO:K04687]
102470650  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
102470906  NR1H3; nuclear receptor subfamily 1 group H member 3 [KO:K08536]
102470940  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
102471054  CLDN18; claudin 18 [KO:K06087]
102471499  TRAF3; TNF receptor associated factor 3 [KO:K03174]
102471654  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
102471776  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102471806  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102472009  CLDN8; claudin 8 [KO:K06087]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472434  CLDN17; claudin 17 [KO:K06087]
102472509  CLDN11; claudin 11 [KO:K06087]
102472740  CTNNB1; catenin beta 1 [KO:K02105]
102472856  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
102472864  CLDN12; claudin 12 [KO:K06087]
102472926  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
102472952  [KO:K05414]
102473925  C8G; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102475056  [KO:K05414]
102475194  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
102475482  [KO:K05414]
102475884  [KO:K05414]
102475979  CLDN23; claudin 23 [KO:K06087]
102476038  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102476089  CLDN15; claudin 15 [KO:K06087]
102476100  CLDN10; claudin 10 [KO:K06087]
102476193  EIF2AK1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102476587  FAS; Fas cell surface death receptor [KO:K04390]
102476590  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102476637  OCLN; occludin [KO:K06088]
102476690  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102476798  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
102477222  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102477389  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102477439  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102477797  BID; BH3 interacting domain death agonist [KO:K04726]
102477904  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
102477989  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102478636  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102479161  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102479406  IFIT1B; interferon-induced protein with tetratricopeptide repeats 1B [KO:K14217]
102479545  [KO:K08738]
102479669  E2F2; E2F transcription factor 2 [KO:K09389]
102479815  IFIT1; interferon-induced protein with tetratricopeptide repeats 1 [KO:K14217]
102480594  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
102480799  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102480854  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
102480902  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102481203  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102482652  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102483469  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
102483700  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102484078  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
102484417  LDLR; low density lipoprotein receptor [KO:K12473]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102484558  TLR3; toll like receptor 3 [KO:K05401]
102484753  CLDN7; claudin 7 [KO:K06087]
102484832  E2F1; E2F transcription factor 1 [KO:K17454]
102485304  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102485560  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
102486539  [KO:K06087]
102486692  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
102487119  [KO:K02187] [EC:3.4.22.56]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102487659  IRF7; interferon regulatory factor 7 [KO:K09447]
102487950  [KO:K04382] [EC:3.1.3.16]
102488182  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
102488324  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
102488432  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102488439  CLDN20; claudin 20 [KO:K06087]
102488449  CLDN16; claudin 16 [KO:K06087]
102488546  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102488678  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102488870  CLDN1; claudin 1 [KO:K06087]
102489673  MX1; MX dynamin like GTPase 1 [KO:K14754]
102489799  FADD; Fas associated via death domain [KO:K02373]
102489835  IRF3; interferon regulatory factor 3 [KO:K05411]
102489942  PSME3; proteasome activator subunit 3 [KO:K06698]
102490080  MX2; MX dynamin like GTPase 2 [KO:K14754]
102490159  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102490423  EGF; epidermal growth factor [KO:K04357]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102490651  CCND1; cyclin D1 [KO:K04503]
102491061  CLDN3; claudin 3 [KO:K06087]
102491473  CLDN4; claudin 4 [KO:K06087]
102492738  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102492983  [KO:K08738]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102493239  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102493291  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102493692  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102493753  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102493858  IFNB1; interferon beta 1 [KO:K05415]
102494136  RNASEL; ribonuclease L [KO:K01165]
102494501  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
102494629  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102495513  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
102495534  IRF9; interferon regulatory factor 9 [KO:K04693]
102495865  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
102495990  CLDN5; claudin 5 [KO:K06087]
102496191  [KO:K08738]
102496359  CLDN14; claudin 14 [KO:K06087]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102497318  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102497973  TNF; tumor necrosis factor [KO:K03156]
102498069  BAD; BCL2 associated agonist of cell death [KO:K02158]
102498195  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
102498355  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
102498386  [KO:K05414]
102498773  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
102498905  CLDN25; claudin 25 [KO:K06087]
102499416  E2F3; E2F transcription factor 3 [KO:K06620]
102499491  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
102499507  RB1; RB transcriptional corepressor 1 [KO:K06618]
102499655  CD81; CD81 molecule [KO:K06508]
102500015  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102500173  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102500394  CLDN6; claudin 6 [KO:K06087]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500801  CLDN9; claudin 9 [KO:K06087]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102501887  [KO:K06698]
102501999  MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102502354  SCARB1; scavenger receptor class B member 1 [KO:K13885]
102502456  CLDN24; putative claudin-24 [KO:K06087]
102502622  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102502878  FASLG; Fas ligand [KO:K04389]
102503238  TP53; tumor protein p53 [KO:K04451]
102503296  [KO:K08738]
102503343  [KO:K08738]
106733204  [KO:K08738]
106733346  [KO:K05414]
106734104  [KO:K08738]
106734874  [KO:K08738]
106735200  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
106735223  [KO:K08738]
106735631  [KO:K08738]
106735729  [KO:K08738]
106735920  [KO:K08738]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup03320  PPAR signaling pathway
tup04010  MAPK signaling pathway
tup04144  Endocytosis
tup04210  Apoptosis
tup04514  Cell adhesion molecules
tup04620  Toll-like receptor signaling pathway
tup04622  RIG-I-like receptor signaling pathway
tup04630  JAK-STAT signaling pathway
tup04668  TNF signaling pathway
KO pathway
ko05160   

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