title: The role of chemokines in acute and chronic hepatitis C infection.
abstract: Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.
authors: Institute of Molecular Medicine, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland.
authors: Stephen
authors: S
authors: Fahey
authors: School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin, Ireland.
authors: Eugene
authors: E
authors: Dempsey
authors: Institute of Molecular Medicine, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin, Ireland.
authors: Aideen
authors: A
authors: Long
mesh_terms: D000818:Animals; D018925:Chemokines / Q000502:physiology*; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000821:virology; D006801:Humans
chemical_list: D018925:Chemokines
references: Exp Biol Med (Maywood). 2011 Jun 1;236(6):637-47
references: 21565895
references: Mem Inst Oswaldo Cruz. 2010 Aug;105(5):611-4
references: 20835605
references: Prog Mol Biol Transl Sci. 2010;97:151-200
references: 21074733
references: FEBS J. 2006 Oct;273(19):4399-407
references: 16965541
references: Int J Biol Markers. 2012 Jul 19;27(2):e125-31
references: 22388957
references: Thromb Haemost. 2007 May;97(5):755-62
references: 17479186
references: PLoS One. 2011;6(9):e24671
references: 21935436
references: J Hepatol. 2010 Nov;53(5):976-80
references: 20800926
references: Hepatology. 2009 Feb;49(2):676-88
references: 19177577
references: Virology. 2002 Nov 25;303(2):253-77
references: 12490388
references: J Infect Dis. 2002 Jun 15;185(12):1803-7
references: 12085329
references: Yonsei Med J. 2011 Nov;52(6):871-8
references: 22028149
references: Br J Cancer. 2006 Jul 17;95(2):210-7
references: 16819541
references: Clin Cancer Res. 2011 Apr 15;17(8):2074-80
references: 21349998
references: Int J Hepatol. 2012;2012:231210
references: 22530132
references: Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G765-71
references: 16282363
references: PLoS One. 2012;7(6):e39486
references: 22745767
references: J Hepatol. 2011 Feb;54(2):357-65
references: 21084131
references: World J Gastroenterol. 2008 Dec 21;14(47):7149-59
references: 19084927
references: Cytokine. 2007 Jul;39(1):50-62
references: 17629707
references: J Clin Invest. 2010 Mar;120(3):907-23
references: 20197626
references: Semin Liver Dis. 2010 Aug;30(3):215-25
references: 20665374
references: Curr Opin Gastroenterol. 2003 Nov;19(6):565-71
references: 15703606
references: Arch Immunol Ther Exp (Warsz). 2002;50(5):307-16
references: 12455864
references: Hepatology. 2006 Sep;44(3):527-35
references: 16941688
references: Nat Immunol. 2008 Sep;9(9):953-9
references: 18711432
references: Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14293-4
references: 22927398
references: Trends Immunol. 2007 Jul;28(7):299-307
references: 17560169
references: Int J Biochem Cell Biol. 2007;39(1):197-205
references: 16973405
references: Physiol Rev. 2009 Oct;89(4):1269-339
references: 19789382
references: PLoS Biol. 2005 Apr;3(4):e113
references: 15799695
references: Int J Cancer. 2010 Mar 1;126(5):1095-108
references: 19642141
references: Hepatology. 2009 Jun;49(6):2055-67
references: 19434726
references: J Exp Med. 2007 Oct 1;204(10):2423-37
references: 17893202
references: Nat Clin Pract Endocrinol Metab. 2009 Jan;5(1):26-34
references: 19079271
references: PLoS Pathog. 2009 Feb;5(2):e1000313
references: 19247441
references: Dig Dis. 2010;28(1):31-44
references: 20460888
references: J Virol. 2007 Jan;81(1):309-18
references: 17035306
references: Nature. 2005 Aug 18;436(7053):946-52
references: 16107834
references: Hepatology. 2008 Jun;47(6):1824-36
references: 18454507
references: Eur Cytokine Netw. 2010 Jun;21(2):99-104
references: 20478763
references: Annu Rev Pharmacol Toxicol. 2008;48:171-97
references: 17883327
references: Am J Physiol Cell Physiol. 2007 Mar;292(3):C987-95
references: 16943240
references: J Virol. 2009 Apr;83(7):2796-802
references: 18842723
references: Hepatology. 2006 Oct;44(4):945-54
references: 17006905
references: Hepatology. 2013 Jan;57(1):331-8
references: 22961770
references: Clin Sci (Lond). 2003 Jan;104(1):47-63
references: 12519087
references: Korean J Hepatol. 2010 Dec;16(4):347-52
references: 21415576
references: Nature. 2005 Aug 18;436(7053):930-2
references: 16107831
references: J Immunol. 2006 Nov 15;177(10):6758-68
references: 17082589
references: Semin Immunopathol. 2009 Sep;31(3):333-43
references: 19639317
references: Dev Immunol. 2002 Sep;9(3):143-9
references: 12885155
references: Immunobiology. 2005;210(2-4):237-47
references: 16164031
references: Hepatology. 2008 Feb;47(2):396-406
references: 18219672
references: Physiol Rev. 2008 Jan;88(1):125-72
references: 18195085
references: Bioinformation. 2010 Oct 06;5(4):166-7
references: 21364780
references: J Hepatol. 2009 May;50(5):980-9
references: 19329213
references: J Gastroenterol. 2008;43(6):419-28
references: 18600385
references: Immunity. 2007 Jan;26(1):117-29
references: 17239632
references: Clin Microbiol Infect. 2011 Feb;17(2):107-15
references: 21091831
references: J Surg Res. 2011 Apr;166(2):241-6
references: 20018298
references: Int J Cancer. 2006 Apr 15;118(8):1869-76
references: 16284949
references: J Leukoc Biol. 2009 Sep;86(3):513-28
references: 19542050
references: Hepatology. 2008 Feb;47(2):729-36
references: 18167066
references: Blood. 2008 Sep 1;112(5):1620-7
references: 18550853
references: Annu Rev Immunol. 2001;19:397-421
references: 11244042
references: Microbiol Immunol. 2005;49(3):265-73
references: 15782000
references: World J Gastroenterol. 2006 Feb 7;12(5):830-1
references: 16521208
references: Eur J Med Res. 2010 Mar 30;15(3):97-101
references: 20452893
references: J Viral Hepat. 2012 Feb;19(2):128-37
references: 22239502
references: J Clin Invest. 2009 Jul;119(7):1858-70
references: 19603542
references: Intern Med. 2006;45(4):183-91
references: 16543687
references: Liver Int. 2011 Feb;31(2):146-62
references: 21073649
references: Nat Rev Immunol. 2003 Jan;3(1):51-62
references: 12511875
references: Dig Dis. 2011;29(4):384-90
references: 21894009
references: Nat Rev Immunol. 2010 Nov;10(11):753-66
references: 20972472
references: Liver Int. 2012 Feb;32(2):339-45
references: 22142261
references: Hepatology. 2004 May;39(5):1220-9
references: 15122750
references: Chem Biol Interact. 2011 Sep 30;193(3):225-31
references: 21803030
references: Blood. 2005 Aug 15;106(4):1175-82
references: 15860662
references: J Antimicrob Chemother. 2004 Jun;53(6):895-8
references: 15128728
references: Hepatology. 2007 Oct;46(4):1279-90
references: 17886338
references: Trends Immunol. 2004 Dec;25(12):677-86
references: 15530839
references: Int J Mol Sci. 2010 Aug 09;11(8):2901-9
references: 21152281
references: J Immunol. 2006 Jul 1;177(1):593-603
references: 16785557
references: Nat Med. 2011 Mar;17(3):252-3
references: 21383718
references: Gut. 2003 Aug;52(8):1075-8
references: 12865260
references: Immunity. 2000 Feb;12(2):121-7
references: 10714678
references: Am J Pathol. 2005 Sep;167(3):887-99
references: 16127166
references: Basic Res Cardiol. 2013 Jan;108(1):310
references: 23184390
references: Cytokine. 2005 Sep 21;31(6):439-46
references: 16105742
references: Autoimmun Rev. 2008 Oct;8(1):18-23
references: 18708169
references: Nat Immunol. 2011 Jun;12(6):500-8
references: 21739673
references: Am J Gastroenterol. 2008 Oct;103(10):2488-94
references: 18775023
references: Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):23-6
references: 15720231
references: J Virol. 2001 Jul;75(13):6209-11
references: 11390624
references: Mol Immunol. 2013 Aug;55(1):94-9
references: 23149103
references: Indian J Med Res. 2009 Nov;130(5):550-5
references: 20090103
references: Gut. 2006 Mar;55(3):374-9
references: 16150856
references: Nat Rev Microbiol. 2007 Jun;5(6):453-63
references: 17487147
references: Biomed Res Int. 2013;2013:187204
references: 23533994
references: Eur J Immunol. 2012 Jan;42(1):17-26
references: 22125159
references: Gastroenterology. 2004 Feb;126(2):529-40
references: 14762790
references: Arterioscler Thromb Vasc Biol. 2008 Nov;28(11):1928-36
references: 18757292
references: Hepatology. 2008 Nov;48(5):1440-50
references: 18798334
references: J Hepatol. 2010 Oct;53(4):752-61
references: 20673595
references: Lancet. 2003 Dec 20;362(9401):2095-100
references: 14697814
references: J Gastrointestin Liver Dis. 2007 Dec;16(4):373-7
references: 18193117
references: Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14562-7
references: 22829669
references: Clin Microbiol Infect. 2011 Feb;17(2):204-9
references: 20219081
references: Z Gastroenterol. 2010 Jan;48(1):38-45
references: 20072995
references: Gastroenterol Res Pract. 2010;2010:971270
references: 21789039
references: J Immunol. 2006 May 15;176(10):6235-44
references: 16670334
references: Immunol Res. 2006;34(3):211-27
references: 16891672
references: Annu Rev Immunol. 2007;25:787-820
references: 17291188
references: J Clin Invest. 2009 Jul;119(7):1745-54
references: 19587449
references: Clin Exp Immunol. 2006 Sep;145(3):535-44
references: 16907924
references: Hepatology. 2011 Jun;53(6):1846-53
references: 21452285
references: Immunol Cell Biol. 2001 Dec;79(6):515-36
references: 11903612
references: J Hepatol. 2003 Jan;38(1):67-75
references: 12480562
references: APMIS. 2007 Jul;115(7):795-801
references: 17614845
references: Circ Res. 2007 Feb 2;100(2):174-90
references: 17272819
references: Clin Sci (Lond). 2007 Feb;112(3):141-55
references: 17199558
references: Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G949-58
references: 12829440
references: Cytokine. 2012 Jan;57(1):25-9
references: 22136974
references: Clin Cancer Res. 2010 Jun 1;16(11):2927-31
references: 20484021
references: Nat Immunol. 2008 Sep;9(9):970-80
references: 18711434
references: Blood. 2005 Feb 15;105(4):1405-7
references: 15498848
references: Hepatology. 2006 Feb;43(2 Suppl 1):S54-62
references: 16447271
references: Annu Rev Immunol. 2009;27:147-63
references: 19302037
references: J Gen Virol. 2008 Feb;89(Pt 2):432-443
references: 18198374
references: Am J Pathol. 2003 Apr;162(4):1249-58
references: 12651617
references: Curr Top Microbiol Immunol. 2006;303:29-46
references: 16570855
references: Nat Rev Immunol. 2007 Sep;7(9):678-89
references: 17717539
references: World J Gastroenterol. 2010 Apr 21;16(15):1832-6
references: 20397259
references: Nature. 2005 Aug 18;436(7053):939-45
references: 16107833
references: J Leukoc Biol. 2011 Nov;90(5):875-82
references: 21750124
references: Arch Pathol Lab Med. 2000 Jul;124(7):1061-5
references: 10888784
references: J Viral Hepat. 2002 May;9(3):213-20
references: 12010510
references: J Autoimmun. 2010 Feb;34(1):1-6
references: 19717280
references: Transl Res. 2007 Mar;149(3):126-36
references: 17320798
references: Nat Rev Immunol. 2011 Sep 23;11(10):658-71
references: 21941294
references: Hepatology. 2011 Feb;53(2):596-603
references: 21274880
references: Gut. 2012 Aug;61(8):1226-34
references: 21873736
references: Scand J Immunol. 2006 Oct;64(4):425-32
references: 16970685
references: Lancet Infect Dis. 2005 Sep;5(9):558-67
references: 16122679
references: Hepatology. 2006 Jul;44(1):126-39
references: 16799989
references: Hepatology. 2004 Jan;39(1):5-19
references: 14752815
references: J Gen Virol. 2008 Oct;89(Pt 10):2507-2517
references: 18796720
references: Microcirculation. 2003 Jun;10(3-4):359-70
references: 12851652
references: Ann Hepatol. 2007 Oct-Dec;6(4):208-13
references: 18007549
references: Clin Exp Immunol. 2008 Nov;154(2):216-23
references: 18778363
references: J Infect Dis. 2006 Oct 1;194(7):895-903
references: 16960776
references: Nature. 2005 Aug 18;436(7053):973-8
references: 16107838
references: Gastroenterology. 2005 Dec;129(6):2064-75
references: 16344072
references: J Virol. 2009 Jan;83(2):836-46
references: 18987152
references: J Clin Invest. 2001 Mar;107(5):595-601
references: 11238560
references: Liver. 2000 Feb;20(1):3-7
references: 10726955
references: PLoS One. 2013 Jun 17;8(6):e66106
references: 23799074
references: J Exp Clin Cancer Res. 2007 Dec;26(4):527-33
references: 18365549
references: Annu Rev Pharmacol Toxicol. 2002;42:469-99
references: 11807180
references: Nat Rev Clin Oncol. 2011 May;8(5):292-301
references: 21386818
references: Clin Dev Immunol. 2012;2012:468107
references: 22611419
references: J Viral Hepat. 2005 Jan;12(1):27-37
references: 15655045
references: J Infect Dis. 2005 Jul 15;192(2):266-75
references: 15962221
references: J Hepatol. 2007 Nov;47(5):632-41
references: 17560677
references: Int J Biol Sci. 2012;8(9):1267-80
references: 23136555
references: PLoS One. 2010 Jun 10;5(6):e11049
references: 20548789
references: J Immunol. 2005 Jan 15;174(2):1055-62
references: 15634930
references: Mediators Inflamm. 2007;2007:67187
references: 17497037
references: Lab Invest. 2000 Mar;80(3):415-22
references: 10744077
references: Blood. 2007 Nov 1;110(9):3447-55
references: 17641205
references: Antiviral Res. 2003 Jun;59(1):1-11
references: 12834855
references: FEMS Microbiol Rev. 2012 May;36(3):663-83
references: 22142141
references: J Viral Hepat. 2011 Sep;18(9):608-18
references: 20565573
references: Gastroenterology. 2003 Oct;125(4):1060-76
references: 14517790
references: Zh Mikrobiol Epidemiol Immunobiol. 2008 Jul-Aug;(4):73-8
references: 18822499
references: BMC Cancer. 2010 Aug 17;10:435
references: 20716344
references: J Virol. 2007 Sep;81(17):9249-58
references: 17567698
references: Diabetologia. 2009 Feb;52(2):281-8
references: 19002429
references: J Surg Res. 2003 Mar;110(1):295-303
references: 12697414
references: AJR Am J Roentgenol. 2005 Mar;184(3):832-41
references: 15728605
references: Eur J Cancer. 2006 Apr;42(6):768-78
references: 16510280
references: Arthritis Rheum. 2007 Jun;56(6):1787-97
references: 17530707
references: BMC Gastroenterol. 2007 Jun 12;7:21
references: 17565659