KEGG   PATHWAY: csab05160
Entry
csab05160                   Pathway                                
Name
Hepatitis C - Chlorocebus sabaeus (green monkey)
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
csab05160  Hepatitis C
csab05160

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103234364  LDLR; low density lipoprotein receptor [KO:K12473]
103239351  SCARB1; scavenger receptor class B member 1 [KO:K13885]
103240440  CD81; CD81 molecule [KO:K06508]
103231581  CLDN34; claudin 34 [KO:K06087]
103236594  putative claudin-24 [KO:K06087]
103241900  CLDN16; claudin 16 [KO:K06087]
103241901  CLDN1; claudin 1 [KO:K06087]
103222999  CLDN5; claudin 5 [KO:K06087]
103246686  CLDN15; claudin 15 [KO:K06087]
103221265  CLDN11; claudin 11 [KO:K06087]
103215361  CLDN23; claudin 23 [KO:K06087]
103242282  CLDN7; claudin 7 [KO:K06087]
103246624  CLDN4; claudin 4 [KO:K06087]
103246626  CLDN3; claudin 3 [KO:K06087]
103241611  CLDN18; claudin 18 [KO:K06087]
103224999  CLDN19; claudin 19 [KO:K06087]
103232448  CLDN2; claudin 2 [KO:K06087]
103217421  CLDN8; claudin 8 [KO:K06087]
103217436  CLDN17; claudin 17 [KO:K06087]
103227077  CLDN9; claudin 9 [KO:K06087]
103227087  CLDN6; claudin 6 [KO:K06087]
103218592  CLDN14; claudin 14 [KO:K06087]
103240760  CLDN20; claudin 20 [KO:K06087]
103248498  CLDN25; claudin 25 [KO:K06087]
103214674  CLDN10; claudin 10 [KO:K06087]
103226577  CLDN12; claudin 12 [KO:K06087]
103222686  OCLN; occludin [KO:K06088]
103239154  OAS1; 2'-5'-oligoadenylate synthetase 1 [KO:K14216] [EC:2.7.7.84]
103239155  OAS3; 2'-5'-oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
103239156  OAS2; 2'-5'-oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
103230468  RNASEL; ribonuclease L [KO:K01165]
103219311  DDX58; DExD/H-box helicase 58 [KO:K12646] [EC:5.6.2.6]
103247611  MAVS; mitochondrial antiviral signaling protein [KO:K12648]
103229744  TRAF3; TNF receptor associated factor 3 [KO:K03174]
103238638  TBK1; TANK binding kinase 1 [KO:K05410] [EC:2.7.11.10]
103230198  IKBKE; inhibitor of nuclear factor kappa B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
103235050  IRF3; interferon regulatory factor 3 [KO:K05411]
103226003  IRF7; interferon regulatory factor 7 [KO:K09447]
103219368  IFNA2; interferon alpha 2 [KO:K05414]
103219366  interferon alpha-1/13-like [KO:K05414]
103219367  IFNA8; interferon alpha 8 [KO:K05414]
103219370  interferon alpha-1/13 [KO:K05414]
103219372  interferon alpha-6 [KO:K05414]
103219377  interferon alpha-14 [KO:K05414]
103219378  interferon alpha-4-like [KO:K05414]
103219379  interferon alpha-4 [KO:K05414]
103219381  interferon alpha-17-like [KO:K05414]
103219383  IFNB1; interferon beta 1 [KO:K05415]
103238673  IFNG; interferon gamma [KO:K04687]
103236634  TLR3; toll like receptor 3 [KO:K05401]
103233731  TICAM1; toll like receptor adaptor molecule 1 [KO:K05842]
103237554  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
103222283  RIPK1; receptor interacting serine/threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
103216382  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103215686  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103232832  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
103228823  NFKBIA; NFKB inhibitor alpha [KO:K04734]
103236047  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103227364  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103235824  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
103237668  eukaryotic translation initiation factor 2-alpha kinase 1-like [KO:K16194] [EC:2.7.11.1]
103246806  EIF2AK1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
103220482  EIF2AK2; eukaryotic translation initiation factor 2 alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
103241350  EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
103245851  EIF2AK4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
103216230  IFIT1; interferon induced protein with tetratricopeptide repeats 1 [KO:K14217]
103216232  IFIT1B; interferon induced protein with tetratricopeptide repeats 1B [KO:K14217]
103237287  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
103229205  EIF2S1; eukaryotic translation initiation factor 2 subunit alpha [KO:K03237]
103243410  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
103243658  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103216875  IFNAR1; interferon alpha and beta receptor subunit 1 [KO:K05130]
103216889  IFNAR2; interferon alpha and beta receptor subunit 2 [KO:K05131]
103224682  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
103234360  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
103217529  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
103238525  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
103228710  IRF9; interferon regulatory factor 9 [KO:K04693]
103219174  MX1; MX dynamin like GTPase 1 [KO:K14754]
103219159  MX2; MX dynamin like GTPase 2 [KO:K14754]
103220885  RSAD2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
103235167  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
103248442  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
103216725  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
103244749  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
103215510  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
103246406  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
103244545  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
103215586  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
103245425  PIAS1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
103236114  EGF; epidermal growth factor [KO:K04357]
103226055  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103243048  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103228953  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103220440  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103246363  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103218763  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103224167  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103227022  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103228031  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103231895  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
103237221  YWHAZ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta [KO:K16197]
103220843  YWHAQ; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
103245470  YWHAB; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein beta [KO:K16197]
103242121  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
103223201  YWHAH; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta [KO:K16198]
103246662  YWHAG; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma [KO:K16198]
103245451  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103233717  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103234391  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103224900  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103222594  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103221212  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103241599  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103225637  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103228213  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103227444  CTNNB1; catenin beta 1 [KO:K02105]
103233293  BAD; BCL2 associated agonist of cell death [KO:K02158]
103221583  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
103242323  TP53; tumor protein p53 [KO:K04451]
103238495  CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
103238589  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
103226555  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
103214406  RB1; RB transcriptional corepressor 1 [KO:K06618]
103248605  E2F1; E2F transcription factor 1 [KO:K17454]
103225395  E2F2; E2F transcription factor 2 [KO:K09389]
103222084  E2F3; E2F transcription factor 3 [KO:K06620]
103218446  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
103233291  TRADD; TNFRSF1A associated via death domain [KO:K03171]
103239600  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
103230577  FASLG; Fas ligand [KO:K04389]
103216224  FAS; Fas cell surface death receptor [KO:K04390]
103245758  FADD; Fas associated via death domain [KO:K02373]
103217637  CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
103236614  CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
103217632  CFLAR; CASP8 and FADD like apoptosis regulator [KO:K04724]
103222876  BID; BH3 interacting domain death agonist [KO:K04726]
103235004  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
103221651  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
103239827  cytochrome c [KO:K08738]
103225665  cytochrome c-like [KO:K08738]
103228018  cytochrome c-like [KO:K08738]
103244190  cytochrome c-like [KO:K08738]
103224843  cytochrome c-like [KO:K08738]
103240990  cytochrome c-like [KO:K08738]
103219556  cytochrome c-like [KO:K08738]
103238923  APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
103225550  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
103243385  PSME3; proteasome activator subunit 3 [KO:K06698]
103239669  RXRA; retinoid X receptor alpha [KO:K08524]
103223491  PPARA; peroxisome proliferator activated receptor alpha [KO:K07294]
103236235  NR1H3; nuclear receptor subfamily 1 group H member 3 [KO:K08536]
103246489  CCND1; cyclin D1 [KO:K04503]
103237430  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
csab03320  PPAR signaling pathway
csab04010  MAPK signaling pathway
csab04144  Endocytosis
csab04210  Apoptosis
csab04514  Cell adhesion molecules
csab04620  Toll-like receptor signaling pathway
csab04622  RIG-I-like receptor signaling pathway
csab04630  JAK-STAT signaling pathway
csab04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

DBGET integrated database retrieval system