title: Induction and evasion of innate antiviral responses by hepatitis C virus.
abstract: Persistent hepatitis C virus infection is associated with progressive hepatic fibrosis and liver cancer. Acute infection evokes several distinct innate immune responses, but these are partially or completely countered by the virus. Hepatitis C virus proteins serve dual functions in replication and immune evasion, acting to disrupt cellular signaling pathways leading to interferon synthesis, subvert Jak-STAT signaling to limit expression of interferon-stimulated genes, and block antiviral activities of interferon-stimulated genes. The net effect is a multilayered evasion of innate immunity, which negatively influences the subsequent development of antigen-specific adaptive immunity, thereby contributing to virus persistence and resistance to therapy.
authors.affiliation: Division of Infectious Disease, Department of Medicine, Center for Translational Immunology, Inflammatory Diseases Institute, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7030, USA.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Lemon
mesh_terms: D000818:Animals; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015398:Signal Transduction / Q000276:immunology
references.citation: Mol Cell Biol. 2009 Sep;29(17):4841-51
references.pmid: 19564419
references.citation: Immunol Rev. 2009 Jan;227(1):75-86
references.pmid: 19120477
references.citation: Gastroenterology. 2006 Nov;131(5):1584-91
references.pmid: 17101330
references.citation: N Engl J Med. 1996 Jan 11;334(2):77-81
references.pmid: 8531962
references.citation: EMBO J. 2006 Jun 7;25(11):2358-67
references.pmid: 16710296
references.citation: J Immunol. 2003 Sep 15;171(6):3154-62
references.pmid: 12960343
references.citation: Hepatology. 2008 Mar;47(3):799-809
references.pmid: 18203148
references.citation: Gastroenterology. 2005 May;128(5):1437-44
references.pmid: 15887125
references.citation: Virology. 1997 Apr 14;230(2):217-27
references.pmid: 9143277
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):985-90
references.pmid: 17215375
references.citation: Nat Immunol. 2004 May;5(5):503-7
references.pmid: 15064760
references.citation: Nat Med. 2004 Dec;10(12):1374-8
references.pmid: 15531891
references.citation: Immunity. 2008 May;28(5):651-61
references.pmid: 18439848
references.citation: J Virol. 2009 Sep;83(17):8463-9
references.pmid: 19553305
references.citation: Nature. 2007 Apr 19;446(7138):916-920
references.pmid: 17392790
references.citation: Science. 2004 Aug 6;305(5685):872-4
references.pmid: 15297676
references.citation: Blood. 2009 Jun 4;113(23):5868-77
references.pmid: 19304955
references.citation: Curr Opin Pharmacol. 2009 Oct;9(5):537-44
references.pmid: 19762279
references.citation: Gastroenterology. 2009 Oct;137(4):1448-58
references.pmid: 19632233
references.citation: EMBO J. 2004 Nov 10;23(22):4384-93
references.pmid: 15510218
references.citation: Hepatology. 2006 Apr;43(4):796-806
references.pmid: 16557551
references.citation: J Virol. 2003 Apr;77(7):3898-912
references.pmid: 12634350
references.citation: Nature. 2008 Jan 31;451(7178):573-7
references.pmid: 18200010
references.citation: Gastroenterology. 2008 Nov;135(5):1710-1718.e2
references.pmid: 18725224
references.citation: Hepatology. 2008 Jul;48(1):322-35
references.pmid: 18506843
references.citation: J Exp Med. 2007 Oct 1;204(10):2423-37
references.pmid: 17893202
references.citation: Immunity. 2009 Jul 17;31(1):25-34
references.pmid: 19576794
references.citation: J Immunol. 2007 Nov 15;179(10):6867-72
references.pmid: 17982077
references.citation: Nat Rev Immunol. 2008 Aug;8(8):594-606
references.pmid: 18641647
references.citation: Science. 2003 May 16;300(5622):1145-8
references.pmid: 12702807
references.citation: Nature. 2009 Sep 17;461(7262):399-401
references.pmid: 19684573
references.citation: Hepatology. 2007 Aug;46(2):558-65
references.pmid: 17526027
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7
references.pmid: 17190814
references.citation: J Biol Chem. 2005 May 27;280(21):20483-92
references.pmid: 15767257
references.citation: Nature. 2006 Jan 12;439(7073):208-11
references.pmid: 16306936
references.citation: J Leukoc Biol. 2007 Sep;82(3):479-87
references.pmid: 17595379
references.citation: Cell. 2005 Sep 9;122(5):669-82
references.pmid: 16125763
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1828-33
references.pmid: 16446426
references.citation: J Biol Chem. 2008 Dec 26;283(52):36211-20
references.pmid: 18984593
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2992-7
references.pmid: 15710891
references.citation: J Virol. 2001 Aug;75(15):7059-66
references.pmid: 11435586
references.citation: Hepatology. 2005 May;41(5):1004-12
references.pmid: 15841462
references.citation: J Interferon Cytokine Res. 2007 Dec;27(12):985-90
references.pmid: 18184038
references.citation: Nat Immunol. 2009 Nov;10(11):1200-7
references.pmid: 19801985
references.citation: Nature. 2001 Oct 18;413(6857):732-8
references.pmid: 11607032
references.citation: Nature. 2008 Jul 24;454(7203):523-7
references.pmid: 18548002
references.citation: Nat Immunol. 2010 Jan;11(1):63-9
references.pmid: 19915568
references.citation: J Hepatol. 2006 Oct;45(4):529-38
references.pmid: 16879891
references.citation: Hepatol Res. 2007 Oct;37 Suppl 3:S319-26
references.pmid: 17931181
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7253-8
references.pmid: 17438296
references.citation: J Gen Virol. 2007 Dec;88(Pt 12):3323-3333
references.pmid: 18024902
references.citation: EMBO J. 2006 Jul 26;25(14):3257-63
references.pmid: 16858409
references.citation: Curr Opin Immunol. 2007 Feb;19(1):1-3
references.pmid: 17157490
references.citation: J Hepatol. 2009 Jul;51(1):29-38
references.pmid: 19443072
references.citation: Hepatol Int. 2008 Jun;2(2):222-30
references.pmid: 19669308
references.citation: Biochimie. 2007 Jun-Jul;89(6-7):729-34
references.pmid: 17367910
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8499-504
references.pmid: 16707574
references.citation: J Virol. 2002 Jun;76(11):5532-9
references.pmid: 11991981
references.citation: Proc Natl Acad Sci U S A. 2008 May 13;105(19):7034-9
references.pmid: 18467494
references.citation: Arch Virol. 2009;154(5):801-10
references.pmid: 19353241
references.citation: Nat Immunol. 2005 Oct;6(10):981-8
references.pmid: 16127453
references.citation: Liver Int. 2010 Feb;30(2):311-8
references.pmid: 19840259
references.citation: Immunity. 2000 Oct;13(4):539-48
references.pmid: 11070172
references.citation: J Clin Invest. 2009 Jul;119(7):1745-54
references.pmid: 19587449
references.citation: Antiviral Res. 2009 Sep;83(3):228-37
references.pmid: 19467267
references.citation: Nature. 2009 Oct 8;461(7265):798-801
references.pmid: 19759533
references.citation: FASEB J. 2003 Mar;17(3):488-90
references.pmid: 12551851
references.citation: Nat Immunol. 2004 Jul;5(7):730-7
references.pmid: 15208624
references.citation: J Biol Chem. 2007 Jul 13;282(28):20047-51
references.pmid: 17502369
references.citation: J Virol. 2009 Oct;83(19):9824-34
references.pmid: 19625408
references.citation: J Virol. 2007 Sep;81(17):8953-66
references.pmid: 17567694
references.citation: Gastroenterology. 2003 May;124(5):1465-75
references.pmid: 12730885
references.citation: Science. 2009 Feb 20;323(5917):1070-4
references.pmid: 19119185
references.citation: J Immunol. 2003 Oct 15;171(8):4304-10
references.pmid: 14530355
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17717-22
references.pmid: 16301520
references.citation: J Gen Virol. 2004 Apr;85(Pt 4):959-969
references.pmid: 15039538
references.citation: Nat Immunol. 2003 Feb;4(2):161-7
references.pmid: 12539043
references.citation: Cell Host Microbe. 2009 Dec 17;6(6):513-22
references.pmid: 20006840
references.citation: J Virol. 2006 Sep;80(18):9226-35
references.pmid: 16940534
references.citation: J Biol Chem. 2007 Mar 09;282(10):7576-81
references.pmid: 17204473
references.citation: Science. 2008 Apr 18;320(5874):379-81
references.pmid: 18420935
references.citation: J Biol Chem. 2007 May 25;282(21):15325-9
references.pmid: 17395583
references.citation: J Biol Chem. 2009 Oct 9;284(41):28343-28351
references.pmid: 19674968
references.citation: J Virol. 2008 Feb;82(4):1665-78
references.pmid: 18077728
references.citation: Nature. 2006 May 4;441(7089):101-5
references.pmid: 16625202
references.citation: J Virol. 2005 Mar;79(5):2689-99
references.pmid: 15708988
references.citation: J Hepatol. 2009 Apr;50(4):705-11
references.pmid: 19231005
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7431-6
references.pmid: 20231459
references.citation: J Virol. 2001 Feb;75(3):1265-73
references.pmid: 11152499
references.citation: J Virol. 2009 Feb;83(3):1299-311
references.pmid: 19036819
references.citation: J Virol. 2007 Jan;81(2):964-76
references.pmid: 17093192
references.citation: J Biol Chem. 2005 Apr 29;280(17):16739-47
references.pmid: 15737993
references.citation: Gastroenterology. 2004 Jan;126(1):263-77
references.pmid: 14699505
references.citation: J Hepatol. 2010 Feb;52(2):167-75
references.pmid: 20006398
references.citation: Nat Struct Mol Biol. 2004 Nov;11(11):1060-7
references.pmid: 15502848
references.citation: Nature. 2005 Oct 20;437(7062):1167-72
references.pmid: 16177806
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):6001-6
references.pmid: 16585524
references.citation: Nat Immunol. 2003 May;4(5):491-6
references.pmid: 12692549
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4650-5
references.pmid: 11904369