KEGG PATHWAY: dnm05160

KEGG

PATHWAY: dnm05160

Entry

dnm05160                    Pathway

Name

Hepatitis C - Dasypus novemcinctus (nine-banded armadillo)

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

Hepatitis C

Organism

Dasypus novemcinctus (nine-banded armadillo) [GN:dnm]

Gene

LDLR; low-density lipoprotein receptor [KO:K12473]

SCARB1; LOW QUALITY PROTEIN: scavenger receptor class B member 1 [KO:K13885]

CD81; CD81 antigen [KO:K06508]

CLDN12; claudin-12 [KO:K06087]

CLDN11; claudin-11 [KO:K06087]

CLDN10; claudin-10 isoform X1 [KO:K06087]

CLDN1; claudin-1 [KO:K06087]

CLDN16; LOW QUALITY PROTEIN: claudin-16 [KO:K06087]

CLDN14; claudin-14 [KO:K06087]

CLDN6; claudin-6 [KO:K06087]

CLDN9; claudin-9 [KO:K06087]

CLDN4; claudin-4 [KO:K06087]

CLDN19; claudin-19 [KO:K06087]

CLDN2; claudin-2 [KO:K06087]

CLDN3; claudin-3 [KO:K06087]

CLDN25; putative claudin-25 [KO:K06087]

CLDN23; claudin-23 [KO:K06087]

CLDN20; claudin-20 [KO:K06087]

CLDN34; claudin-34 [KO:K06087]

CLDN18; claudin-18 isoform X1 [KO:K06087]

CLDN5; claudin-5 [KO:K06087]

CLDN7; claudin-7 [KO:K06087]

claudin-17 [KO:K06087]

CLDN22; claudin-22 [KO:K06087]

putative claudin-24 [KO:K06087]

CLDN15; claudin-15 [KO:K06087]

OCLN; occludin [KO:K06088]

OAS1; 2'-5'-oligoadenylate synthase 1 [KO:K14216] [EC:2.7.7.84]

RNASEL; 2-5A-dependent ribonuclease isoform X1 [KO:K01165]

DDX58; LOW QUALITY PROTEIN: probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]

basic proline-rich protein-like [KO:K12648]

TRAF3; TNF receptor-associated factor 3 [KO:K03174]

TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]

IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]

IRF3; interferon regulatory factor 3 [KO:K05411]

IRF7; interferon regulatory factor 7 [KO:K09447]

interferon alpha-2-like [KO:K05414]

interferon alpha-3-like [KO:K05414]

interferon alpha-2-like [KO:K05414]

interferon alpha-2-like [KO:K05414]

interferon alpha-2-like [KO:K05414]

interferon alpha-2-like [KO:K05414]

IFNB1; interferon beta [KO:K05415]

IFNG; interferon gamma [KO:K04687]

TLR3; toll-like receptor 3 [KO:K05401]

TICAM1; TIR domain-containing adapter molecule 1 [KO:K05842]

TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]

RIPK1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]

CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]

IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]

IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]

NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]

NFKB1; LOW QUALITY PROTEIN: nuclear factor NF-kappa-B p105 subunit [KO:K02580]

RELA; transcription factor p65 [KO:K04735]

TNF; tumor necrosis factor [KO:K03156]

CXCL10; C-X-C motif chemokine 10 [KO:K12671]

EIF2AK1; eukaryotic translation initiation factor 2-alpha kinase 1 isoform X1 [KO:K16194] [EC:2.7.11.1]

EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]

EIF2AK3; eukaryotic translation initiation factor 2-alpha kinase 3 isoform X3 [KO:K08860] [EC:2.7.11.1]

EIF2AK4; eIF-2-alpha kinase GCN2 [KO:K16196] [EC:2.7.11.1]

LOW QUALITY PROTEIN: interferon-induced protein with tetratricopeptide repeats 1B-like [KO:K14217]

interferon-induced protein with tetratricopeptide repeats 1-like isoform X1 [KO:K14217]

LOW QUALITY PROTEIN: interferon-induced protein with tetratricopeptide repeats 1B [KO:K14217]

EIF3E; eukaryotic translation initiation factor 3 subunit E [KO:K03250]

EIF2S1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]

STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]

SOCS3; suppressor of cytokine signaling 3 [KO:K04696]

IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]

IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]

JAK1; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]

TYK2; LOW QUALITY PROTEIN: non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]

STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]

STAT2; signal transducer and activator of transcription 2 [KO:K11221]

IRF9; interferon regulatory factor 9 [KO:K04693]

MX1; interferon-induced GTP-binding protein Mx1 [KO:K14754]

RSAD2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]

PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X4 [KO:K03456]

LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]

PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]

PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]

PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]

PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X3 [KO:K04354]

PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]

PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]

PIAS1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]

EGF; pro-epidermal growth factor isoform X1 [KO:K04357]

EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]

GRB2; growth factor receptor-bound protein 2 [KO:K04364]

SOS2; son of sevenless homolog 2 [KO:K03099]

HRAS; GTPase HRas isoform X1 [KO:K02833]

KRAS; GTPase KRas isoform X4 [KO:K07827]

NRAS; GTPase NRas [KO:K07828]

LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]

BRAF; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]

RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]

ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]

YWHAQ; 14-3-3 protein theta [KO:K16197]

YWHAZ; 14-3-3 protein zeta/delta [KO:K16197]

YWHAB; 14-3-3 protein beta/alpha [KO:K16197]

14-3-3 protein beta/alpha [KO:K16197]

YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]

YWHAG; 14-3-3 protein gamma [KO:K16198]

YWHAH; 14-3-3 protein eta [KO:K16198]

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]

dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]

PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]

PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]

PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]

PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]

PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]

AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]

AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]

AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]

GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]

CTNNB1; catenin beta-1 [KO:K02105]

BAD; bcl2-associated agonist of cell death [KO:K02158]

CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]

TP53; cellular tumor antigen p53 [KO:K04451]

CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]

CDK4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]

CDK6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]

LOW QUALITY PROTEIN: retinoblastoma-associated protein [KO:K06618]

E2F2; transcription factor E2F2 isoform X1 [KO:K09389]

E2F3; transcription factor E2F3 [KO:K06620]

TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]

TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]

TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]

FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]

FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]

FADD; FAS-associated death domain protein [KO:K02373]

CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]

CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]

CFLAR; CASP8 and FADD-like apoptosis regulator isoform X2 [KO:K04724]

BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]

BAX; apoptosis regulator BAX [KO:K02159]

BAK1; bcl-2 homologous antagonist/killer [KO:K14021]

cytochrome c-like [KO:K08738]

cytochrome c-like [KO:K08738]

cytochrome c [KO:K08738]

cytochrome c-like [KO:K08738]

cytochrome c-like [KO:K08738]

cytochrome c [KO:K08738]

cytochrome c [KO:K08738]

cytochrome c-like [KO:K08738]

APAF1; apoptotic protease-activating factor 1 isoform X2 [KO:K02084]

CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]

proteasome activator complex subunit 3 [KO:K06698]

PSME3; LOW QUALITY PROTEIN: proteasome activator complex subunit 3 [KO:K06698]

RXRA; retinoic acid receptor RXR-alpha isoform X2 [KO:K08524]

PPARA; peroxisome proliferator-activated receptor alpha isoform X4 [KO:K07294]

NR1H3; oxysterols receptor LXR-alpha isoform X1 [KO:K08536]

CCND1; G1/S-specific cyclin-D1 [KO:K04503]

MYC; myc proto-oncogene protein isoform X1 [KO:K04377]

Compound

Phosphatidylinositol-3,4,5-trisphosphate

2-5A

Reference

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PPAR signaling pathway

MAPK signaling pathway

Endocytosis

Apoptosis

Cell adhesion molecules

Toll-like receptor signaling pathway

RIG-I-like receptor signaling pathway

JAK-STAT signaling pathway

TNF signaling pathway

KO pathway

LinkDB

DBGET integrated database retrieval system