KEGG   PATHWAY: rno05160
Entry
rno05160                    Pathway                                

Name
Hepatitis C - Rattus norvegicus (rat)
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
rno05160  Hepatitis C
rno05160

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
300438  Ldlr; low-density lipoprotein receptor precursor [KO:K12473]
25073  Scarb1; scavenger receptor class B member 1 [KO:K13885]
25621  Cd81; CD81 antigen [KO:K06508]
290485  Cldn10; claudin-10 [KO:K06087]
290789  Cldn23; claudin-23 [KO:K06087]
298487  Cldn19; claudin-19 [KO:K06087]
300920  Cldn2; claudin-2 [KO:K06087]
304073  Cldn14; claudin-14 [KO:K06087]
304124  Cldn8; claudin-8 [KO:K06087]
304125  Cldn17; claudin-17 [KO:K06087]
304388  Cldn15; claudin-15 [KO:K06087]
304407  Cldn4; claudin-4 [KO:K06087]
306454  Cldn22; claudin-22 [KO:K06087]
315953  Cldn18; claudin-18 precursor [KO:K06087]
65129  Cldn1; claudin-1 [KO:K06087]
65130  Cldn3; claudin-3 [KO:K06087]
65131  Cldn5; claudin-5 [KO:K06087]
84588  Cldn11; claudin-11 [KO:K06087]
100361422  Cldn34c4; claudin-34 [KO:K06087]
155268  Cldn16; claudin-16 [KO:K06087]
287098  Cldn6; claudin-6 precursor [KO:K06087]
287099  Cldn9; claudin-9 [KO:K06087]
680178  Cldn20; claudin-20 precursor [KO:K06087]
65132  Cldn7; claudin-7 precursor [KO:K06087]
680489  Cldn34e; uncharacterized protein LOC680489 [KO:K06087]
680370  Cldn34d; claudin 34D [KO:K06087]
502083  Cldn24; putative claudin-24 [KO:K06087]
100360390  Cldn25; putative claudin-25 [KO:K06087]
83497  Ocln; occludin [KO:K06088]
192281  Oas1a; 2'-5'-oligoadenylate synthase 1A [KO:K14216] [EC:2.7.7.84]
363938  Oas2; 2'-5'-oligoadenylate synthase 2 [KO:K14216] [EC:2.7.7.84]
494202  Oas3; 2'-5'-oligoadenylate synthase 3 [KO:K14216] [EC:2.7.7.84]
246268  Oas1b; inactive 2'-5'-oligoadenylate synthase 1B [KO:K14216] [EC:2.7.7.84]
304507  Oas1i; 2 ' -5 ' oligoadenylate synthetase 1I [KO:K14216] [EC:2.7.7.84]
359726  Rnasel; 2-5A-dependent ribonuclease [KO:K01165]
297989  Ddx58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:3.6.4.13]
311430  Mavs; mitochondrial antiviral-signaling protein [KO:K12648]
362788  Traf3; TNF receptor-associated factor 3 [KO:K03174]
299827  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
292892  Irf3; interferon regulatory factor 3 [KO:K05411]
293624  Irf7; interferon regulatory factor 7 [KO:K09447]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha-5 [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  RGD1559679; interferon alpha-1-like [KO:K05414]
500491  Ifna16l1; interferon alpha-1-like [KO:K05414]
24481  Ifnb1; interferon beta precursor [KO:K05415]
25712  Ifng; interferon gamma precursor [KO:K04687]
364594  Tlr3; toll-like receptor 3 precursor [KO:K05401]
363328  Ticam1; TIR domain-containing adapter molecule 1 isoform X1 [KO:K05842]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
306886  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
24835  Tnf; tumor necrosis factor [KO:K03156]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
27137  Eif2ak1; eukaryotic translation initiation factor 2-alpha kinase 1 [KO:K16194] [EC:2.7.11.1]
54287  Eif2ak2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
29702  Eif2ak3; eukaryotic translation initiation factor 2-alpha kinase 3 precursor [KO:K08860] [EC:2.7.11.1]
114859  Eif2ak4; eIF-2-alpha kinase GCN2 [KO:K16196] [EC:2.7.11.1]
56824  Ifit1; interferon-induced protein with tetratricopeptide repeats 1-like protein [KO:K14217]
294090  Ifit1bl; interferon-induced protein with tetratricopeptide repeats 1 isoform X2 [KO:K14217]
299872  Eif3el1; eukaryotic translation initiation factor 3 subunit E [KO:K03250]
54318  Eif2s1; eukaryotic translation initiation factor 2 subunit 1 [KO:K03237]
25125  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
89829  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
288264  Ifnar1; interferon alpha/beta receptor 1 isoform 1 precursor [KO:K05130]
686326  Ifnar2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
305896  Irf9; interferon regulatory factor 9 [KO:K04693]
286918  Mx2; interferon-induced GTP-binding protein Mx2 [KO:K14754]
24575  Mx1; interferon-induced GTP-binding protein Mx1 [KO:K14754]
65190  Rsad2; radical S-adenosyl methionine domain-containing protein 2 [KO:K15045]
117281  Ppp2r1a; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
315648  Ppp2r1b; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
246255  Ppp2r2d; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
60660  Ppp2r2b; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
117256  Ppp2r2c; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
117104  Ppp2r2a; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
24672  Ppp2ca; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
24673  Ppp2cb; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
300772  Pias1; E3 SUMO-protein ligase PIAS1 [KO:K04706] [EC:2.3.2.-]
25313  Egf; pro-epidermal growth factor precursor [KO:K04357]
24329  Egfr; epidermal growth factor receptor precursor [KO:K04361] [EC:2.7.10.1]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
114486  Braf; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:2.7.11.1]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
64363  Araf; serine/threonine-protein kinase A-Raf isoform 1 [KO:K08845] [EC:2.7.11.1]
25578  Ywhaz; 14-3-3 protein zeta/delta [KO:K16197]
56011  Ywhab; 14-3-3 protein beta/alpha [KO:K16197]
25577  Ywhaq; 14-3-3 protein theta [KO:K16197]
29753  Ywhae; 14-3-3 protein epsilon [KO:K06630]
25576  Ywhah; 14-3-3 protein eta [KO:K16198]
56010  Ywhag; 14-3-3 protein gamma [KO:K16198]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84353  Ctnnb1; catenin beta-1 [KO:K02105]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
114851  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
362817  Cdk2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
94201  Cdk4; cyclin-dependent kinase 4 [KO:K02089] [EC:2.7.11.22]
114483  Cdk6; cyclin-dependent kinase 6 [KO:K02091] [EC:2.7.11.22]
24708  Rb1; retinoblastoma-associated protein [KO:K06618]
399489  E2f1; transcription factor E2F1 [KO:K17454]
684111  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
291105  E2f3; transcription factor E2F3 [KO:K06620]
25625  Tnfrsf1a; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
246756  Tradd; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
311786  Traf2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
25385  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
246097  Fas; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
117279  Cflar; CASP8 and FADD-like apoptosis regulator isoform 1 [KO:K04724]
64625  Bid; BH3-interacting domain death agonist [KO:K04726]
24887  Bax; apoptosis regulator BAX [KO:K02159]
116502  Bak1; bcl-2 homologous antagonist/killer [KO:K14021]
25309  Cycs; cytochrome c, somatic [KO:K08738]
25310  Cyct; cytochrome c, testis-specific [KO:K08738]
100363502  cytochrome c, somatic [KO:K08738]
78963  Apaf1; apoptotic protease-activating factor 1 [KO:K02084]
58918  Casp9; caspase-9 [KO:K04399] [EC:3.4.22.62]
287716  Psme3; proteasome activator complex subunit 3 [KO:K06698]
25271  Rxra; retinoic acid receptor RXR-alpha [KO:K08524]
25747  Ppara; peroxisome proliferator-activated receptor alpha [KO:K07294]
58852  Nr1h3; oxysterols receptor LXR-alpha [KO:K08536]
58919  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
24577  Myc; myc proto-oncogene protein [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
rno03320  PPAR signaling pathway
rno04010  MAPK signaling pathway
rno04144  Endocytosis
rno04210  Apoptosis
rno04514  Cell adhesion molecules
rno04620  Toll-like receptor signaling pathway
rno04622  RIG-I-like receptor signaling pathway
rno04630  JAK-STAT signaling pathway
rno04668  TNF signaling pathway
KO pathway
ko05160   

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