KEGG   PATHWAY: ptg05160
Entry
ptg05160                    Pathway                                
Name
Hepatitis C - Panthera tigris altaica (Amur tiger)
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
ptg05160  Hepatitis C
ptg05160

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102949981  LDLR; low density lipoprotein receptor [KO:K12473]
102962792  SCARB1; scavenger receptor class B member 1 [KO:K13885]
102955269  CD81; CD81 molecule [KO:K06508]
102966840  CLDN34; claudin 34 [KO:K06087]
102963508  CLDN4; claudin-4 [KO:K06087]
102950622  CLDN15; claudin 15 [KO:K06087]
102966696  CLDN8; claudin 8 [KO:K06087]
102972126  CLDN17; claudin 17 [KO:K06087]
102951915  CLDN25; claudin 25 [KO:K06087]
102959345  CLDN11; claudin 11 [KO:K06087]
102951466  CLDN19; claudin 19 [KO:K06087]
102970408  CLDN24; claudin 24 [KO:K06087]
102949581  CLDN22; claudin-22 [KO:K06087]
102972664  putative claudin-24 [KO:K06087]
102949704  CLDN16; claudin 16 [KO:K06087]
102949998  CLDN1; claudin 1 [KO:K06087]
102953242  CLDN14; claudin 14 [KO:K06087]
102953046  CLDN7; claudin 7 [KO:K06087]
102965254  CLDN2; claudin 2 [KO:K06087]
102970552  claudin-7-like [KO:K06087]
102953578  CLDN10; claudin 10 [KO:K06087]
102955873  CLDN20; claudin 20 [KO:K06087]
102964426  CLDN9; claudin 9 [KO:K06087]
102968286  CLDN18; claudin 18 [KO:K06087]
102956058  CLDN12; claudin 12 [KO:K06087]
102948707  OCLN; occludin [KO:K06088]
102952232  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
107179395  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
102963811  RNASEL; ribonuclease L [KO:K01165]
102953066  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:5.6.2.6]
102963414  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
102952767  TRAF3; TNF receptor associated factor 3 [KO:K03174]
102960158  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
102963614  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
102956602  IRF3; interferon regulatory factor 3 [KO:K05411]
102956750  interferon alpha-2-like [KO:K05414]
102960421  IFNB1; interferon beta 1 [KO:K05415]
102963756  IFNG; interferon gamma [KO:K04687]
102972168  TLR3; toll like receptor 3 [KO:K05401]
102951327  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
102960157  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102964459  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
102949289  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102963734  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102956127  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102964232  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102951132  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102958919  TNF; tumor necrosis factor [KO:K03156]
102956896  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
102950763  EIF2AK1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
102951575  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
102963843  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
102970603  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
102952624  IFIT1; interferon-induced protein with tetratricopeptide repeats 1 [KO:K14217]
102953087  IFIT1B; interferon induced protein with tetratricopeptide repeats 1B [KO:K14217]
102960214  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
102962011  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
102957987  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
102955444  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
102954859  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
102960189  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102953204  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102953174  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102967399  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102955306  IRF9; interferon regulatory factor 9 [KO:K04693]
102971334  MX1; interferon-induced GTP-binding protein Mx1 [KO:K14754]
102956399  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
102968462  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
102951141  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102961543  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102970289  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102949872  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102951261  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
102952971  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102956715  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102954008  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102949895  PIAS1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
102959656  EGF; epidermal growth factor [KO:K04357]
102967370  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102970459  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102949403  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102950748  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102951082  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102956086  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
102962314  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
102966103  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
102960626  14-3-3 protein zeta/delta-like [KO:K16197]
102948901  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
102960323  14-3-3 protein epsilon [KO:K06630]
102970295  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102965301  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
102972607  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102961382  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102959570  CTNNB1; catenin beta 1 [KO:K02105]
102956027  BAD; BCL2 associated agonist of cell death [KO:K02158]
102964051  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
102962571  TP53; tumor protein p53 [KO:K04451]
102959572  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102970281  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
102967948  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
102952365  RB1; RB transcriptional corepressor 1 [KO:K06618]
102963506  E2F1; E2F transcription factor 1 [KO:K17454]
102952251  E2F2; E2F transcription factor 2 [KO:K09389]
102948948  E2F3; E2F transcription factor 3 [KO:K06620]
102956793  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102968597  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102966802  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102953222  FASLG; Fas ligand [KO:K04389]
102958442  FAS; Fas cell surface death receptor [KO:K04390]
102962460  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
102954729  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
102963219  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
102951809  BID; BH3 interacting domain death agonist [KO:K04726]
102949153  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102970767  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
102966744  cytochrome c 2-like [KO:K08738]
102952864  cytochrome c-like [KO:K08738]
102960081  cytochrome c [KO:K08738]
102964536  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
102967404  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
102963671  PSME3; proteasome activator subunit 3 [KO:K06698]
102971837  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
102961389  NR1H3; nuclear receptor subfamily 1 group H member 3 [KO:K08536]
102959906  CCND1; cyclin D1 [KO:K04503]
102954147  MYC; v-myc avian myelocytomatosis viral oncogene homolog [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
ptg03320  PPAR signaling pathway
ptg04010  MAPK signaling pathway
ptg04144  Endocytosis
ptg04210  Apoptosis
ptg04514  Cell adhesion molecules
ptg04620  Toll-like receptor signaling pathway
ptg04622  RIG-I-like receptor signaling pathway
ptg04630  JAK-STAT signaling pathway
ptg04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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