KEGG PATHWAY: ko05160

PATHWAY: ko05160

Entry

ko05160                     Pathway

Name

Hepatitis C

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

ko05160

Hepatitis C

Disease

H00413

Hepatitis C

Drug

D00423

Ribavirin (JP18/USP/INN)

D03433

Celgosivir hydrochloride (USAN)

D03501

Ciluprevir (USAN/INN)

D06651

Taribavirin hydrochloride (USAN)

D08876

Boceprevir (INN/USAN)

D08951

Nesbuvir (USAN)

D09012

Telaprevir (JAN/USAN/INN)

D09028

Valopicitabine dihydrochloride (USAN)

D09582

Balapiravir (USAN/INN)

D09583

Balapiravir hydrochloride (USAN)

D09616

Filibuvir (USAN/INN)

D09644

Narlaprevir (USAN/INN)

D09884

Danoprevir (USAN/INN)

D09885

Danoprevir sodium (USAN)

D09971

Tegobuvir (USAN/INN)

D09987

Vaniprevir (JAN/USAN/INN)

D10065

Daclatasvir (USAN)

D10081

Simeprevir (JAN/USAN)

D10093

Asunaprevir (JAN/USAN)

D10105

Daclatasvir dihydrochloride (USAN)

D10165

Setrobuvir (USAN)

D10166

Sovaprevir (USAN)

D10366

Sofosbuvir (JAN/USAN/INN)

D10393

Deldeprevir (USAN/INN)

D10394

Deldeprevir sodium (USAN)

D10408

Vedroprevir (USAN/INN)

D10425

Lomibuvir (USAN/INN)

D10442

Ledipasvir (USAN/INN)

D10462

Faldaprevir sodium (JAN/USAN)

D10469

Simeprevir sodium (JAN)

D10477

Mericitabine (USAN/INN)

D10553

Dasabuvir (USAN/INN)

D10554

Deleobuvir (USAN/INN)

D10576

Ombitasvir (USAN/INN)

D10578

Ledipasvir and sofosbuvir

D10580

Paritaprevir (USAN/INN)

D10581

Dasabuvir sodium hydrate

D10582

Dasabuvir, ombitasvir, paritaprevir and ritonavir

D10597

Paritaprevir hydrate (JAN)

D10598

Ombitasvir hydrate (JAN)

D10599

Ledipasvir acetonate (JAN)

D10610

Beclabuvir (USAN/INN)

D10611

Beclabuvir hydrochloride (JAN/USAN)

D10622

Deleobuvir sodium (JAN/USAN)

D10625

Elbasvir (JAN/USAN/INN)

D10639

Grazoprevir (USAN)

D10665

Samatasvir (USAN/INN)

D10745

Ombitasvir, paritaprevir and ritonavir

D10778

Elbasvir and grazoprevir

D10806

Velpatasvir (JAN/USAN/INN)

D10814

Glecaprevir (USAN/INN)

D10815

Glecaprevir hydrate (JAN)

D10816

Pibrentasvir (JAN/USAN/INN)

D10882

Daclatasvir, asunaprevir and beclabuvir

D10899

Voxilaprevir (USAN/INN)

D10900

Sofosbuvir, velpatasvir and voxilaprevir

D10996

Uprifosbuvir (USAN/INN)

D11217

Ruzasvir (USAN/INN)

D11364

Adafosbuvir (USAN)

D11565

Grazoprevir (USAN/INN)

D12247

Coblopasvir (INN)

D12255

Bemnifosbuvir (USAN)

D12260

Bemnifosbuvir sulfate (USAN)

D12744

Ravidasvir (USAN/INN)

D12745

Ravidasvir hydrochloride (USAN)

Orthology

K12473

low-density lipoprotein receptor

K22272

Hepatitis C virus envelope glycoprotein E2

K13885

scavenger receptor class B, member 1

K06508

CD81 antigen

K06087

claudin

K06088

occludin

K24861

Hepatitis C virus envelope glycoprotein E1

K22497

Hepatitis C virus non-structural protein 2 [EC:3.4.22.-]

K22273

Hepatitis C virus serine protease / helicase NS3 [EC:3.4.21.98 3.6.1.15 5.6.2.6]

K22274

Hepatitis C virus non-structural protein 4A

K22498

Hepatitis C virus non-structural protein 4B

K22275

Hepatitis C virus non-structural protein 5A

K22472

Hepatitis C virus RNA-dependent RNA polymerase [EC:2.7.7.48]

K14216

2'-5'-oligoadenylate synthetase [EC:2.7.7.84]

K01165

ribonuclease L

K12646

ATP-dependent RNA helicase DDX58 [EC:5.6.2.6]

K12648

mitochondrial antiviral-signaling protein

K03174

TNF receptor-associated factor 3

K05410

TANK-binding kinase 1 [EC:2.7.11.10]

K07211

inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]

K05411

interferon regulatory factor 3

K09447

interferon regulatory factor 7

K05414

interferon alpha

K05415

interferon beta

K04687

interferon gamma

K05401

toll-like receptor 3

K05842

toll-like receptor adapter molecule 1

K03175

TNF receptor-associated factor 6 [EC:2.3.2.27]

K02861

receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1]

K04467

inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]

K07209

inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]

K07210

inhibitor of nuclear factor kappa-B kinase subunit gamma

K04734

NF-kappa-B inhibitor alpha

K02580

nuclear factor NF-kappa-B p105 subunit

K04735

transcription factor p65

K03156

tumor necrosis factor superfamily, member 2

K12671

C-X-C motif chemokine 10

K16194

eukaryotic translation initiation factor 2-alpha kinase 1 [EC:2.7.11.1]

K16195

eukaryotic translation initiation factor 2-alpha kinase 2 [EC:2.7.11.1]

K08860

eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]

K16196

eukaryotic translation initiation factor 2-alpha kinase 4 [EC:2.7.11.1]

K22271

Hepatitis C virus core protein

K14217

interferon-induced protein with tetratricopeptide repeats 1

K03250

translation initiation factor 3 subunit E

K03237

translation initiation factor 2 subunit 1

K04692

signal transducer and activator of transcription 3

K04696

suppressor of cytokine signaling 3

K05130

interferon receptor 1

K05131

interferon receptor 2

K11217

Janus kinase 1 [EC:2.7.10.2]

K11219

non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]

K11220

signal transducer and activator of transcription 1

K11221

signal transducer and activator of transcription 2

K04693

interferon regulatory factor 9

K14754

interferon-induced GTP-binding protein Mx

K15045

radical S-adenosyl methionine domain-containing protein 2

K03456

serine/threonine-protein phosphatase 2A regulatory subunit A

K04354

serine/threonine-protein phosphatase 2A regulatory subunit B

K04382

serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16]

K04706

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

K04357

epidermal growth factor

K04361

epidermal growth factor receptor [EC:2.7.10.1]

K04364

growth factor receptor-bound protein 2

K03099

son of sevenless

K02833

GTPase HRas

K07827

GTPase KRas

K07828

GTPase NRas

K04365

B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04366

RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K08845

A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K16197

14-3-3 protein beta/theta/zeta

K06630

14-3-3 protein epsilon

K16198

14-3-3 protein gamma/eta

K04368

mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K02649

phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K00922

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K04456

RAC serine/threonine-protein kinase [EC:2.7.11.1]

K03083

glycogen synthase kinase 3 beta [EC:2.7.11.26]

K02105

catenin beta 1

K02158

Bcl-2-antagonist of cell death

K06625

cyclin-dependent kinase inhibitor 1A

K04451

tumor protein p53

K02206

cyclin-dependent kinase 2 [EC:2.7.11.22]

K02089

cyclin-dependent kinase 4 [EC:2.7.11.22]

K02091

cyclin-dependent kinase 6 [EC:2.7.11.22]

K06618

retinoblastoma-associated protein

K17454

transcription factor E2F1

K09389

transcription factor E2F2

K06620

transcription factor E2F3

K03158

tumor necrosis factor receptor superfamily member 1A

K03171

tumor necrosis factor receptor type 1-associated DEATH domain protein

K03173

TNF receptor-associated factor 2 [EC:2.3.2.27]

K04389

tumor necrosis factor ligand superfamily member 6

K04390

tumor necrosis factor receptor superfamily member 6

K02373

FAS-associated death domain protein

K04398

caspase 8 [EC:3.4.22.61]

K02187

caspase 3 [EC:3.4.22.56]

K04724

CASP8 and FADD-like apoptosis regulator

K04726

BH3 interacting domain death agonist

K02159

apoptosis regulator BAX

K14021

Bcl-2 homologous antagonist/killer

K08738

cytochrome c

K02084

apoptotic protease-activating factor

K04399

caspase 9 [EC:3.4.22.62]

K06698

proteasome activator subunit 3 (PA28 gamma)

K08524

retinoid X receptor alpha

K07294

peroxisome proliferator-activated receptor alpha

K08536

liver X receptor alpha

K04503

G1/S-specific cyclin-D1

K04377

Myc proto-oncogene protein

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

ko03320