KEGG   PATHWAY: pcoq05160
Entry
pcoq05160                   Pathway                                
Name
Hepatitis C - Propithecus coquereli (Coquerel's sifaka)
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
pcoq05160  Hepatitis C
pcoq05160

Disease
H00413  Hepatitis C
Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105804948  E2F1; transcription factor E2F1 [KO:K17454]
105805081  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105805737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105806012  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 isoform X1 [KO:K16194] [EC:2.7.11.1]
105806202  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
105806240  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105806352  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
105806400  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
105806705  CLDN16; LOW QUALITY PROTEIN: claudin-16 [KO:K06087]
105806737  RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
105806742  YWHAQ; 14-3-3 protein theta [KO:K16197]
105806767  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
105806853  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
105806896  MX1; interferon-induced GTP-binding protein Mx1 isoform X1 [KO:K14754]
105806899  CLDN14; claudin-14 [KO:K06087]
105806974  CLDN11; claudin-11 isoform X1 [KO:K06087]
105807025  YWHAG; 14-3-3 protein gamma [KO:K16198]
105807081  CLDN4; claudin-4 [KO:K06087]
105807086  CLDN3; claudin-3 [KO:K06087]
105807375  [KO:K08738]
105807545  KRAS; GTPase KRas [KO:K07827]
105807810  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
105807852  LDLR; low-density lipoprotein receptor [KO:K12473]
105808396  IFNG; interferon gamma [KO:K04687]
105808709  CLDN1; claudin-1 [KO:K06087]
105809316  BAX; apoptosis regulator BAX [KO:K02159]
105809375  IRF3; interferon regulatory factor 3 [KO:K05411]
105809563  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105809776  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
105810089  TLR3; toll-like receptor 3 [KO:K05401]
105810111  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
105810199  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105810299  EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X1 [KO:K08860] [EC:2.7.11.1]
105810397  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105810555  [KO:K08738]
105810591  NRAS; GTPase NRas [KO:K07828]
105810783  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105811098  NR1H3; oxysterols receptor LXR-alpha isoform X1 [KO:K08536]
105811180  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
105811323  MYC; myc proto-oncogene protein [KO:K04377]
105811483  CLDN2; claudin-2 [KO:K06087]
105811926  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
105811965  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105812249  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105812313  CLDN19; claudin-19 isoform X1 [KO:K06087]
105812404  CLDN20; claudin-20 [KO:K06087]
105812509  [KO:K08738]
105812606  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105812625  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
105812737  IRF9; interferon regulatory factor 9 isoform X1 [KO:K04693]
105812779  CLDN10; claudin-10 isoform X1 [KO:K06087]
105813135  CLDN6; claudin-6 [KO:K06087]
105813136  CLDN9; claudin-9 [KO:K06087]
105813290  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
105813707  RB1; retinoblastoma-associated protein [KO:K06618]
105813802  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105813943  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105814042  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105814229  CLDN34; claudin 34 [KO:K06087]
105814498  EIF2AK4; eukaryotic translation initiation factor 2-alpha kinase 4 isoform X1 [KO:K16196] [EC:2.7.11.1]
105814571  TRAF6; LOW QUALITY PROTEIN: TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
105814677  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105814744  CLDN23; claudin-23 [KO:K06087]
105815609  [KO:K08738]
105815699  E2F2; transcription factor E2F2 [KO:K09389]
105815749  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
105815816  BID; BH3-interacting domain death agonist [KO:K04726]
105815896  [KO:K03237]
105816012  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
105816051  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
105816513  CD81; CD81 antigen [KO:K06508]
105816561  HRAS; GTPase HRas isoform X1 [KO:K02833]
105816570  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
105816738  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
105816815  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105817095  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
105817322  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105817351  YWHAE; 14-3-3 protein epsilon [KO:K06630]
105817905  TNF; tumor necrosis factor isoform X1 [KO:K03156]
105818006  SOS1; son of sevenless homolog 1 [KO:K03099]
105818017  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase isoform X1 [KO:K16195] [EC:2.7.11.1]
105818191  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105818690  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
105818840  CLDN5; claudin-5 [KO:K06087]
105818935  EGF; pro-epidermal growth factor [KO:K04357]
105819002  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105819191  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105819376  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
105819395  TP53; cellular tumor antigen p53 [KO:K04451]
105819401  CFLAR; CASP8 and FADD-like apoptosis regulator [KO:K04724]
105819427  CLDN7; claudin-7 [KO:K06087]
105819477  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
105819684  DDX58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:3.6.4.13]
105819687  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105819858  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
105820132  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
105820208  PSME3; proteasome activator complex subunit 3 [KO:K06698]
105820249  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
105820591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105820771  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
105820798  CLDN8; claudin-8 [KO:K06087]
105820812  CLDN17; claudin-17 [KO:K06087]
105820833  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
105820890  CLDN22; claudin-22 [KO:K06087]
105820894  CLDN24; putative claudin-24 [KO:K06087]
105821114  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
105821217  [KO:K07211] [EC:2.7.11.10]
105821252  YWHAB; 14-3-3 protein beta/alpha [KO:K16197]
105821415  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
105821530  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105821578  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
105821684  BAK1; bcl-2 homologous antagonist/killer isoform X1 [KO:K14021]
105822194  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
105822246  CLDN25; putative claudin-25 [KO:K06087]
105822648  IFIT1B; LOW QUALITY PROTEIN: interferon-induced protein with tetratricopeptide repeats 1B [KO:K14217]
105822691  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105822724  IFIT1; interferon-induced protein with tetratricopeptide repeats 1 [KO:K14217]
105823104  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105823286  YWHAH; 14-3-3 protein eta [KO:K16198]
105823400  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
105824014  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105824183  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
105824261  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
105824538  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105824793  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105824997  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105825008  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105825276  [KO:K04354]
105825335  CTNNB1; catenin beta-1 [KO:K02105]
105825562  SCARB1; scavenger receptor class B member 1 [KO:K13885]
105825595  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
105825853  SOS2; son of sevenless homolog 2 [KO:K03099]
105826002  CLDN18; claudin-18 isoform X1 [KO:K06087]
105826040  CLDN15; claudin-15 [KO:K06087]
105826075  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
105826393  [KO:K06087]
105826394  [KO:K06087]
105826540  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105826612  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105826638  OCLN; occludin [KO:K06088]
105826705  RXRA; retinoic acid receptor RXR-alpha [KO:K08524]
105826802  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
105827001  [KO:K05414]
105827006  IFNB1; interferon beta [KO:K05415]
105827094  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
105827296  BAD; bcl2-associated agonist of cell death [KO:K02158]
105827383  RELA; transcription factor p65 isoform X1 [KO:K04735]
105827423  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
105827473  FADD; FAS-associated death domain protein [KO:K02373]
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
pcoq03320  PPAR signaling pathway
pcoq04010  MAPK signaling pathway
pcoq04144  Endocytosis
pcoq04210  Apoptosis
pcoq04514  Cell adhesion molecules
pcoq04620  Toll-like receptor signaling pathway
pcoq04622  RIG-I-like receptor signaling pathway
pcoq04630  JAK-STAT signaling pathway
pcoq04668  TNF signaling pathway
KO pathway
ko05160   

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