KEGG   PATHWAY: ppam05160
Entry
ppam05160                   Pathway                                
Name
Hepatitis C - Pteronotus mesoamericanus (Parnell's mustached bat)
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
ppam05160  Hepatitis C
ppam05160

Organism
Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]
Gene
129061362  LDLR; low-density lipoprotein receptor [KO:K12473]
129087161  SCARB1; scavenger receptor class B member 1 isoform X1 [KO:K13885]
129068497  CD81; CD81 antigen [KO:K06508]
129069086  CLDN19; claudin-19 [KO:K06087]
129063449  CLDN12; claudin-12 [KO:K06087]
129083376  CLDN9; claudin-9 [KO:K06087]
129083377  CLDN6; claudin-6 [KO:K06087]
129083419  CLDN3; claudin-3 [KO:K06087]
129083444  CLDN15; claudin-15 [KO:K06087]
129076959  CLDN34; claudin-34 [KO:K06087]
129083773  CLDN4; claudin-4 [KO:K06087]
129064690  CLDN23; claudin-23 [KO:K06087]
129064706  putative claudin-24 [KO:K06087]
129064707  CLDN22; claudin-22 [KO:K06087]
129072323  CLDN7; claudin-7 [KO:K06087]
129072395  CLDN17; claudin-17 [KO:K06087]
129072410  CLDN8; claudin-8 [KO:K06087]
129072591  CLDN14; claudin-14 [KO:K06087]
129086139  CLDN25; LOW QUALITY PROTEIN: putative claudin-25 [KO:K06087]
129086225  CLDN5; claudin-5 [KO:K06087]
129073238  CLDN2; claudin-2 [KO:K06087]
129073330  CLDN11; claudin-11 [KO:K06087]
129079879  CLDN1; claudin-1 [KO:K06087]
129079981  CLDN16; LOW QUALITY PROTEIN: claudin-16 [KO:K06087]
129080936  CLDN10; claudin-10 isoform X1 [KO:K06087]
129087838  CLDN18; claudin-18 isoform X1 [KO:K06087]
129067867  CLDN20; claudin-20 [KO:K06087]
129074601  OCLN; occludin [KO:K06088]
129085425  2'-5'-oligoadenylate synthase 1-like [KO:K14216] [EC:2.7.7.84]
129087190  OAS1; LOW QUALITY PROTEIN: 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]
129087369  OAS3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
129087432  OAS2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
129081878  RNASEL; 2-5A-dependent ribonuclease [KO:K01165]
129078222  RIGI; antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
129070825  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
129066167  TRAF3; TNF receptor-associated factor 3 [KO:K03174]
129075846  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
129062348  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
129082940  IRF3; interferon regulatory factor 3 [KO:K05411]
129073150  IRF7; interferon regulatory factor 7 [KO:K09447]
129078455  LOW QUALITY PROTEIN: interferon alpha-4-like [KO:K05414]
129078454  IFNB1; interferon beta [KO:K05415]
129076046  IFNG; interferon gamma [KO:K04687]
129064878  TLR3; toll-like receptor 3 [KO:K05401]
129078173  TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]
129080456  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
129085546  RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
129077110  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129064790  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
129074378  IKBKG; NF-kappa-B essential modulator [KO:K07210]
129082066  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129085322  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129068571  RELA; transcription factor p65 [KO:K04735]
129066972  TNF; tumor necrosis factor [KO:K03156]
129083964  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
129067359  EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 isoform X1 [KO:K16194] [EC:2.7.11.1]
129066240  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
129085559  EIF2AK3; LOW QUALITY PROTEIN: eukaryotic translation initiation factor 2-alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
129064361  EIF2AK4; eIF-2-alpha kinase GCN2 isoform X1 [KO:K16196] [EC:2.7.11.1]
129069759  interferon-induced protein with tetratricopeptide repeats 1B-like [KO:K14217]
129069999  interferon-induced protein with tetratricopeptide repeats 1-like [KO:K14217]
129070000  interferon-induced protein with tetratricopeptide repeats 1-like isoform X1 [KO:K14217]
129084276  EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
129065952  EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
129086937  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
129086506  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
129074194  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
129074177  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
129071023  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
129061567  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
129065467  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
129075775  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
129074057  IRF9; interferon regulatory factor 9 [KO:K04693]
129074642  MX2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
129074657  MX1; interferon-induced GTP-binding protein Mx1 isoform X1 [KO:K14754]
129067783  RSAD2; S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 [KO:K15045]
129081552  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
129086002  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
129075024  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
129077675  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
129066572  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
129079776  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
129064836  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
129066683  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
129064148  PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
129085287  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129068919  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129086587  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129064134  son of sevenless homolog 2 isoform X1 [KO:K03099]
129066034  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129073113  HRAS; GTPase HRas isoform X1 [KO:K02833]
129084969  KRAS; GTPase KRas isoform X1 [KO:K07827]
129063946  NRAS; GTPase NRas [KO:K07828]
129062984  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129088423  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129065223  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
129070674  YWHAB; 14-3-3 protein beta/alpha isoform X1 [KO:K16197]
129084246  YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]
129067683  YWHAQ; 14-3-3 protein theta [KO:K16197]
129070343  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
129083794  YWHAG; 14-3-3 protein gamma [KO:K16198]
129087483  YWHAH; 14-3-3 protein eta [KO:K16198]
129064157  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129078155  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129078069  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129086248  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129074969  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129069407  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129074590  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129075675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129076577  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129088291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129076641  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129066231  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129073033  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129069640  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129088214  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
129068612  BAD; bcl2-associated agonist of cell death [KO:K02158]
129067419  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129072290  TP53; cellular tumor antigen p53 [KO:K04451]
129075823  CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
129063507  CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
129080865  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129070474  E2F1; transcription factor E2F1 [KO:K17454]
129068981  E2F2; transcription factor E2F2 [KO:K09389]
129085787  E2F3; transcription factor E2F3 [KO:K06620]
129071418  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
129075095  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
129079528  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
129081899  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
129069755  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
129068522  FADD; FAS-associated death domain protein [KO:K02373]
129080711  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
129064891  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
129080428  CFLAR; CASP8 and FADD-like apoptosis regulator isoform X1 [KO:K04724]
129081160  BID; BH3-interacting domain death agonist [KO:K04726]
129082924  BAX; apoptosis regulator BAX [KO:K02159]
129066993  BAK1; bcl-2 homologous antagonist/killer [KO:K14021]
129082218  cytochrome c-like [KO:K08738]
129062822  cytochrome c [KO:K08738]
129083450  cytochrome c-like [KO:K08738]
129084433  cytochrome c-like [KO:K08738]
129071395  APAF1; apoptotic protease-activating factor 1 [KO:K02084]
129075586  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129086882  PSME3; proteasome activator complex subunit 3 [KO:K06698]
129079171  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
129077896  PPARA; peroxisome proliferator-activated receptor alpha isoform X1 [KO:K07294]
129081432  NR1H3; oxysterols receptor LXR-alpha isoform X1 [KO:K08536]
129068523  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129084081  MYC; myc proto-oncogene protein [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
ppam03320  PPAR signaling pathway
ppam04010  MAPK signaling pathway
ppam04144  Endocytosis
ppam04210  Apoptosis
ppam04514  Cell adhesion molecules
ppam04620  Toll-like receptor signaling pathway
ppam04622  RIG-I-like receptor signaling pathway
ppam04630  JAK-STAT signaling pathway
ppam04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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