KEGG   PATHWAY: mmu05160
Entry
mmu05160                    Pathway                                
Name
Hepatitis C - Mus musculus (house mouse)
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
mmu05160  Hepatitis C
mmu05160

Organism
Mus musculus (house mouse) [GN:mmu]
Gene
16835  Ldlr; low density lipoprotein receptor [KO:K12473]
20778  Scarb1; scavenger receptor class B, member 1 [KO:K13885]
12520  Cd81; CD81 antigen [KO:K06508]
73934  Cldn34c4; claudin 34C4 [KO:K06087]
74987  Cldn34d; claudin 34D [KO:K06087]
114141  Cldn16; claudin 16 [KO:K06087]
12737  Cldn1; claudin 1 [KO:K06087]
12738  Cldn2; claudin 2 [KO:K06087]
12739  Cldn3; claudin 3 [KO:K06087]
12740  Cldn4; claudin 4 [KO:K06087]
12741  Cldn5; claudin 5 [KO:K06087]
18417  Cldn11; claudin 11 [KO:K06087]
239931  Cldn17; claudin 17 [KO:K06087]
242653  Cldn19; claudin 19 [KO:K06087]
53624  Cldn7; claudin 7 [KO:K06087]
54419  Cldn6; claudin 6 [KO:K06087]
54420  Cldn8; claudin 8 [KO:K06087]
56173  Cldn14; claudin 14 [KO:K06087]
56492  Cldn18; claudin 18 [KO:K06087]
56863  Cldn9; claudin 9 [KO:K06087]
57255  Cldn13; claudin 13 [KO:K06087]
58187  Cldn10; claudin 10 [KO:K06087]
60363  Cldn15; claudin 15 [KO:K06087]
71908  Cldn23; claudin 23 [KO:K06087]
621628  Cldn20; claudin 20 [KO:K06087]
75677  Cldn22; claudin 22 [KO:K06087]
628893  Cldn34-ps; claudin 34, pseudogene [KO:K06087]
100039801  Cldn24; claudin 24 [KO:K06087]
64945  Cldn12; claudin 12 [KO:K06087]
100042785  Cldn25; claudin 25 [KO:K06087]
18260  Ocln; occludin [KO:K06088]
246730  Oas1a; 2'-5' oligoadenylate synthetase 1A [KO:K14216] [EC:2.7.7.84]
246728  Oas2; 2'-5' oligoadenylate synthetase 2 [KO:K14216] [EC:2.7.7.84]
246727  Oas3; 2'-5' oligoadenylate synthetase 3 [KO:K14216] [EC:2.7.7.84]
23961  Oas1b; 2'-5' oligoadenylate synthetase 1B [KO:K14216] [EC:2.7.7.84]
23960  Oas1g; 2'-5' oligoadenylate synthetase 1G [KO:K14216] [EC:2.7.7.84]
24014  Rnasel; ribonuclease L (2', 5'-oligoisoadenylate synthetase-dependent) [KO:K01165]
230073  Rigi; RNA sensor RIG-I [KO:K12646] [EC:5.6.2.6]
228607  Mavs; mitochondrial antiviral signaling protein [KO:K12648]
22031  Traf3; TNF receptor-associated factor 3 [KO:K03174]
56480  Tbk1; TANK-binding kinase 1 [KO:K05410] [EC:2.7.11.10]
56489  Ikbke; inhibitor of kappaB kinase epsilon [KO:K07211] [EC:2.7.11.10]
54131  Irf3; interferon regulatory factor 3 [KO:K05411]
54123  Irf7; interferon regulatory factor 7 [KO:K09447]
15962  Ifna1; interferon alpha 1 [KO:K05414]
15965  Ifna2; interferon alpha 2 [KO:K05414]
15967  Ifna4; interferon alpha 4 [KO:K05414]
15968  Ifna5; interferon alpha 5 [KO:K05414]
15969  Ifna6; interferon alpha 6 [KO:K05414]
15970  Ifna7; interferon alpha 7 [KO:K05414]
15972  Ifna9; interferon alpha 9 [KO:K05414]
15964  Ifna11; interferon alpha 11 [KO:K05414]
242519  Ifna12; interferon alpha 12 [KO:K05414]
230396  Ifna13; interferon alpha 13 [KO:K05414]
404549  Ifna14; interferon alpha 14 [KO:K05414]
15974  Ifnab; interferon alpha B [KO:K05414]
242517  Ifna15; interferon alpha 15 [KO:K05414]
230398  Ifna16; interferon alpha 16 [KO:K05414]
15977  Ifnb1; interferon beta 1, fibroblast [KO:K05415]
15978  Ifng; interferon gamma [KO:K04687]
142980  Tlr3; toll-like receptor 3 [KO:K05401]
106759  Ticam1; TIR domain containing adaptor molecule 1 [KO:K05842]
22034  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
19766  Ripk1; receptor (TNFRSF)-interacting serine-threonine kinase 1 [KO:K02861] [EC:2.7.11.1]
12675  Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
16150  Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]
16151  Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]
18035  Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]
18033  Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]
19697  Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]
21926  Tnf; tumor necrosis factor [KO:K03156]
15945  Cxcl10; C-X-C motif chemokine ligand 10 [KO:K12671]
15467  Eif2ak1; eukaryotic translation initiation factor 2 alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
19106  Eif2ak2; eukaryotic translation initiation factor 2-alpha kinase 2 [KO:K16195] [EC:2.7.11.1]
13666  Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
27103  Eif2ak4; eukaryotic translation initiation factor 2 alpha kinase 4 [KO:K16196] [EC:2.7.11.1]
112419  Ifit1bl2; interferon induced protein with tetratricopeptide repeats 1B like 2 [KO:K14217]
15957  Ifit1; interferon-induced protein with tetratricopeptide repeats 1 [KO:K14217]
667373  Ifit1bl1; interferon induced protein with tetratricpeptide repeats 1B like 1 [KO:K14217]
16341  Eif3e; eukaryotic translation initiation factor 3, subunit E [KO:K03250]
13665  Eif2s1; eukaryotic translation initiation factor 2, subunit 1 alpha [KO:K03237]
20848  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
12702  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
15975  Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]
15976  Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]
16451  Jak1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
54721  Tyk2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
20846  Stat1; signal transducer and activator of transcription 1 [KO:K11220]
20847  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
16391  Irf9; interferon regulatory factor 9 [KO:K04693]
17858  Mx2; MX dynamin-like GTPase 2 [KO:K14754]
17857  Mx1; MX dynamin-like GTPase 1 [KO:K14754]
58185  Rsad2; radical S-adenosyl methionine domain containing 2 [KO:K15045]
51792  Ppp2r1a; protein phosphatase 2, regulatory subunit A, alpha [KO:K03456]
73699  Ppp2r1b; protein phosphatase 2, regulatory subunit A, beta [KO:K03456]
52432  Ppp2r2d; protein phosphatase 2, regulatory subunit B, delta [KO:K04354]
72930  Ppp2r2b; protein phosphatase 2, regulatory subunit B, beta [KO:K04354]
269643  Ppp2r2c; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
71978  Ppp2r2a; protein phosphatase 2, regulatory subunit B, alpha [KO:K04354]
19052  Ppp2ca; protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform [KO:K04382] [EC:3.1.3.16]
19053  Ppp2cb; protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform [KO:K04382] [EC:3.1.3.16]
56469  Pias1; protein inhibitor of activated STAT 1 [KO:K04706] [EC:2.3.2.-]
13645  Egf; epidermal growth factor [KO:K04357]
13649  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
14784  Grb2; growth factor receptor bound protein 2 [KO:K04364]
20662  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
20663  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
15461  Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  Nras; neuroblastoma ras oncogene [KO:K07828]
109880  Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
11836  Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
22631  Ywhaz; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide [KO:K16197]
54401  Ywhab; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide [KO:K16197]
22630  Ywhaq; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta [KO:K16197]
100039786  Gm2423; predicted gene 2423 [KO:K16197]
22627  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon polypeptide [KO:K06630]
22629  Ywhah; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide [KO:K16198]
22628  Ywhag; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma polypeptide [KO:K16198]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
56637  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
12387  Ctnnb1; catenin beta 1 [KO:K02105]
12015  Bad; BCL2-associated agonist of cell death [KO:K02158]
12575  Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]
22059  Trp53; transformation related protein 53 [KO:K04451]
12566  Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
12567  Cdk4; cyclin dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
12571  Cdk6; cyclin dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
19645  Rb1; RB transcriptional corepressor 1 [KO:K06618]
13555  E2f1; E2F transcription factor 1 [KO:K17454]
242705  E2f2; E2F transcription factor 2 [KO:K09389]
13557  E2f3; E2F transcription factor 3 [KO:K06620]
21937  Tnfrsf1a; tumor necrosis factor receptor superfamily, member 1a [KO:K03158]
71609  Tradd; TNFRSF1A-associated via death domain [KO:K03171]
22030  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
14103  Fasl; Fas ligand [KO:K04389]
14102  Fas; Fas cell surface death receptor [KO:K04390]
14082  Fadd; Fas associated via death domain [KO:K02373]
12370  Casp8; caspase 8 [KO:K04398] [EC:3.4.22.61]
12367  Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
12633  Cflar; CASP8 and FADD-like apoptosis regulator [KO:K04724]
12122  Bid; BH3 interacting domain death agonist [KO:K04726]
12028  Bax; BCL2-associated X protein [KO:K02159]
12018  Bak1; BCL2-antagonist/killer 1 [KO:K14021]
13063  Cycs; cytochrome c, somatic [KO:K08738]
13067  Cyct; cytochrome c, testis [KO:K08738]
11783  Apaf1; apoptotic peptidase activating factor 1 [KO:K02084]
12371  Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]
19192  Psme3; proteaseome (prosome, macropain) activator subunit 3 (PA28 gamma, Ki) [KO:K06698]
20181  Rxra; retinoid X receptor alpha [KO:K08524]
19013  Ppara; peroxisome proliferator activated receptor alpha [KO:K07294]
22259  Nr1h3; nuclear receptor subfamily 1, group H, member 3 [KO:K08536]
12443  Ccnd1; cyclin D1 [KO:K04503]
17869  Myc; myelocytomatosis oncogene [KO:K04377]
Compound
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C20935  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
mmu03320  PPAR signaling pathway
mmu04010  MAPK signaling pathway
mmu04144  Endocytosis
mmu04210  Apoptosis
mmu04514  Cell adhesion molecules
mmu04620  Toll-like receptor signaling pathway
mmu04622  RIG-I-like receptor signaling pathway
mmu04630  JAK-STAT signaling pathway
mmu04668  TNF signaling pathway
KO pathway
ko05160   
LinkDB

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