Innate immune responses in hepatitis C virus infection

Seminars in Immunopathology

Volumn 35, Issue 1, 2013, Pages 53-72

  Li, Kui ^a   Lemon, Stanley M ^b  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Hepatitis C virus; Immune evasion; Interferon; Interferon stimulated gene; JaK STAT pathway; RIG I; Toll like receptor

Indexed keywords

2',5' OLIGOADENYLATE SYNTHETASE; ADENOSINE DEAMINASE; ALPHA INTERFERON; CYTOKINE; GAMMA INTERFERON; GUANINE NUCLEOTIDE BINDING PROTEIN; INTERFERON; INTERFERON RECEPTOR; INTERFERON REGULATORY FACTOR; INTERFERON REGULATORY FACTOR 1; INTERFERON REGULATORY FACTOR 7; JANUS KINASE 1; JANUS KINASE 2; PATTERN RECOGNITION RECEPTOR; PEGINTERFERON; PHOSPHOPROTEIN PHOSPHATASE 2A; PROTEIN ADAR1; PROTEIN GBP1; PROTEIN ISG20; PROTEIN KINASE R; PROTEIN P56; RETINOIC ACID INDUCIBLE PROTEIN I; RIBAVIRIN; S ADENOSYLMETHIONINE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 8; UNCLASSIFIED DRUG;

ADAPTIVE IMMUNITY; ANTIVIRAL ACTIVITY; CYTOKINE PRODUCTION; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IMMUNE EVASION; IMMUNOREGULATION; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN SYNTHESIS INHIBITION; REVIEW; SIGNAL TRANSDUCTION; VIRAL CLEARANCE; VIRUS PATHOGENESIS;

HEPACIVIRUS; HEPATITIS C; HUMANS; IMMUNE EVASION; IMMUNITY, INNATE; INTERFERONS; RECEPTORS, RETINOIC ACID; TOLL-LIKE RECEPTOR 3;

EID: 84872396542     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-012-0332-x     Document Type: Review

References (187)

1. Abe T, Kaname Y, Hamamoto I, Tsuda Y, Wen X, Taguwa S, Moriishi K, Takeuchi O, Kawai T, Kanto T, Hayashi N, Akira S, Matsuura Y (2007) Hepatitis C virus nonstructural protein 5A modulates the Toll-like receptor-MyD88-dependent signaling pathway in macrophage cell lines. J Virol 81:8953-8966
2. Ait-Goughoulte M, Kanda T, Meyer K, Ryerse JS, Ray RB, Ray R (2008) Hepatitis C virus genotype 1a growth and induction of autophagy. J Virol 82:2241-2249
3. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413:732-738
4. Aly HH, Watashi K, Hijikata M, Kaneko H, Takada Y, Egawa H, Uemoto S, Shimotohno K (2007) Serum-derived hepatitis C virus infectivity in interferon regulatory factor-7-suppressed human primary hepatocytes. J Hepatol 46:26-36
5. Arnaud N, Dabo S, Maillard P, Budkowska A, Kalliampakou KI, Mavromara P, Garcin D, Hugon J, Gatignol A, Akazawa D, Wakita T, Meurs EF (2010) Hepatitis C virus controls interferon production through PKR activation. PLoS One 5:e10575
6. Arnaud N, Dabo S, Akazawa D, Fukasawa M, Shinkai-Ouchi F, Hugon J, Wakita T, Meurs EF (2011) Hepatitis C virus reveals a novel early control in acute immune response. PLoS Pathog 7:e1002289
7. Barry G, Breakwell L, Fragkoudis R, Attarzadeh-Yazdi G, Rodriguez-Andres J, Kohl A, Fazakerley JK (2009) PKR acts early in infection to suppress Semliki Forest virus production and strongly enhances the type I interferon response. J Gen Virol 90:1382-1391
8. Bellecave P, Sarasin-Filipowicz M, Donze O, Kennel A, Gouttenoire J, Meylan E, Terracciano L, Tschopp J, Sarrazin C, Berg T, Moradpour D, Heim MH (2010) Cleavage of mitochondrial antiviral signaling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system. Hepatology 51:1127-1136
9. Berzsenyi MD, Roberts SK, Preiss S, Woollard DJ, Beard MR, Skinner NA, Bowden DS, Visvanathan K (2011) Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-alpha in HCV & HCV/HIV infection. J Viral Hepat 18:852-860
10. Bigger CB, Brasky KM, Lanford RE (2001) DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection. J Virol 75:7059-7066
11. Blindenbacher A, Duong FH, Hunziker L, Stutvoet ST, Wang X, Terracciano L, Moradpour D, Blum HE, Alonzi T, Tripodi M, La Monica N, Heim MH (2003) Expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology 124:1465-1475
12. Bode JG, Ludwig S, Ehrhardt C, Albrecht U, Erhardt A, Schaper F, Heinrich PC, Haussinger D (2003) IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J 17:488-490
13. Bode JG, Brenndorfer ED, Haussinger D (2007) Subversion of innate host antiviral strategies by the hepatitis C virus. Arch Biochem Biophys 462:254-265
14. Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, Stark GR (2007) Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov 6:975-990
15. Botos I, Liu L, Wang Y, Segal DM, Davies DR (2009) The Toll-like receptor 3:dsRNA signaling complex. Biochim Biophys Acta 1789:667-674
16. Bowen DG, Walker CM (2005) Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 436:946-952
17. Branch AD, Stump DD, Gutierrez JA, Eng F, Walewski JL (2005) The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others. Semin Liver Dis 25:105-117
18. Breiman A, Grandvaux N, Lin R, Ottone C, Akira S, Yoneyama M, Fujita T, Hiscott J, Meurs EF (2005) Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J Virol 79:3969-3978
19. Carpentier PA, Williams BR, Miller SD (2007) Distinct roles of protein kinase R and Toll-like receptor 3 in the activation of astrocytes by viral stimuli. Glia 55:239-252
20. Chang KS, Cai Z, Zhang C, Sen GC, Williams BR, Luo G (2006) Replication of hepatitis C virus (HCV) RNA in mouse embryonic fibroblasts: protein kinase R (PKR)-dependent and PKR-independent mechanisms for controlling HCV RNA replication and mediating interferon activities. J Virol 80:7364-7374
21. Chang JH, Kato N, Muroyama R, Taniguchi H, Guleng B, Dharel N, Shao RX, Tateishi K, Jazag A, Kawabe T, Omata M (2010) Double-stranded RNA-activated protein kinase inhibits hepatitis C virus replication but may be not essential in interferon treatment. Liver Int 30:311-318
22. Chen L, Borozan I, Feld J, Sun J, Tannis LL, Coltescu C, Heathcote J, Edwards AM, McGilvray ID (2005) Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 128:1437-1444
23. Chen Z, Benureau Y, Rijnbrand R, Yi J, Wang T, Warter L, Lanford RE, Weinman SA, Lemon SM, Martin A, Li K (2007) GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. J Virol 81:964-976
24. Chen L, Li S, McGilvray I (2011) The ISG15/USP18 ubiquitin-like pathway (ISGylation system) in hepatitis C virus infection and resistance to interferon therapy. Int J Biochem Cell Biol 43:1427-1431
25. Cheng G, Zhong J, Chisari FV (2006) Inhibition of dsRNA-induced signaling in hepatitis C virus-infected cells by NS3 protease-dependent and -independent mechanisms. Proc Natl Acad Sci USA 103:8499-8504
26. Christen V, Treves S, Duong FH, Heim MH (2007) Activation of endoplasmic reticulum stress response by hepatitis viruses up-regulates protein phosphatase 2A. Hepatology 46:558-565
27. Coccia EM, Severa M, Giacomini E, Monneron D, Remoli ME, Julkunen I, Cella M, Lande R, Uze G (2004) Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells. Eur J Immunol 34:796-805
28. Daffis S, Samuel MA, Suthar MS, Gale M Jr, Diamond MS (2008) Toll-like receptor 3 has a protective role against West Nile virus infection. J Virol 82:10349-10358
29. Dansako H, Ikeda M, Kato N (2007) Limited suppression of the interferon-beta production by hepatitis C virus serine protease in cultured human hepatocytes. FEBS J 274:4161-4176
30. de Lucas S, Bartolome J, Carreno V (2005) Hepatitis C virus core protein down-regulates transcription of interferon-induced antiviral genes. J Infect Dis 191:93-99
31. Degols G, Eldin P, Mechti N (2007) ISG20, an actor of the innate immune response. Biochimie 89:831-835
32. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141:668-681
33. Dolganiuc A, Kodys K, Kopasz A, Marshall C, Do T, Romics L Jr, Mandrekar P, Zapp M, Szabo G (2003) Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol 170:5615-5624
34. Dolganiuc A, Oak S, Kodys K, Golenbock DT, Finberg RW, Kurt-Jones E, Szabo G (2004) Hepatitis C core and nonstructural 3 proteins trigger Toll-like receptor 2-mediated pathways and inflammatory activation. Gastroenterology 127:1513-1524
35. Dreux M, Gastaminza P, Wieland SF, Chisari FV (2009) The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci USA 106:14046-14051
36. Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MH (2004) Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology 126:263-277
37. Duong FH, Christen V, Filipowicz M, Heim MH (2006) S-Adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro. Hepatology 43:796-806
38. Dustin LB, Rice CM (2007) Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol 25:71-99
39. Egger D, Wolk B, Gosert R, Bianchi L, Blum HE, Moradpour D, Bienz K (2002) Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol 76:5974-5984
40. Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, Izumi N (1996) Interferon sensitivity determining sequence of the hepatitis C virus genome. Hepatology 24:460
41. Ferraris P, Blanchard E, Roingeard P (2010) Ultrastructural and biochemical analyses of hepatitis C virus-associated host cell membranes. J Gen Virol 91:2230-2237
42. Ferreon JC, Ferreon AC, Li K, Lemon SM (2005) Molecular determinants of TRIF proteolysis mediated by the hepatitis C virus NS3/4A protease. J Biol Chem 280:20483-20492
43. Foy E, Li K, Wang C, Sumpter R Jr, Ikeda M, Lemon SM, Gale M Jr (2003) Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300:1145-1148
44. Fredericksen BL, Keller BC, Fornek J, Katze MG, Gale M Jr (2008) Establishment and maintenance of the innate antiviral response to West Nile virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol 82:609-616
45. Frese M, Schwarzle V, Barth K, Krieger N, Lohmann V, Mihm S, Haller O, Bartenschlager R (2002) Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology 35:694-703
46. Funami K, Matsumoto M, Oshiumi H, Akazawa T, Yamamoto A, Seya T (2004) The cytoplasmic 'linker region' in Toll-like receptor 3 controls receptor localization and signaling. Int Immunol 16:1143-1154
47. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, Takeuchi O, Akira S, Chen Z, Inoue S, Jung JU (2007) TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446:916-920
48. Gale MJ Jr, Korth MJ, Tang NM, Tan SL, Hopkins DA, Dever TE, Polyak SJ, Gretch DR, Katze MG (1997) Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein. Virology 230:217-227
49. Gale M Jr, Blakely CM, Kwieciszewski B, Tan SL, Dossett M, Tang NM, Korth MJ, Polyak SJ, Gretch DR, Katze MG (1998) Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation. Mol Cell Biol 18:5208-5218
50. Gao L, Aizaki H, He JW, Lai MM (2004) Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft. J Virol 78:3480-3488
51. Garaigorta U, Chisari FV (2009) Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation. Cell Host Microbe 6:513-522
52. George CX, Gan Z, Liu Y, Samuel CE (2011) Adenosine deaminases acting on RNA, RNA editing, and interferon action. J Interferon Cytokine Res 31:99-117
53. Gilfoy FD, Mason PW (2007) West Nile virus-induced interferon production is mediated by the double-stranded RNA-dependent protein kinase PKR. J Virol 81:11148-11158
54. Gosert R, Egger D, Lohmann V, Bartenschlager R, Blum HE, Bienz K, Moradpour D (2003) Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 77:5487-5492
55. Guo J, Hui DJ, Merrick WC, Sen GC (2000) A new pathway of translational regulation mediated by eukaryotic initiation factor 3. EMBO J 19:6891-6899
56. Guo JT, Bichko VV, Seeger C (2001) Effect of alpha interferon on the hepatitis C virus replicon. J Virol 75:8516-8523
57. Han JQ, Barton DJ (2002) Activation and evasion of the antiviral 2′-5′ oligoadenylate synthetase/ribonuclease L pathway by hepatitis C virus mRNA. RNA 8:512-525
58. Hardarson HS, Baker JS, Yang Z, Purevjav E, Huang CH, Alexopoulou L, Li N, Flavell RA, Bowles NE, Vallejo JG (2007) Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am J Physiol Heart Circ Physiol 292:H251-H258
59. He B (2006) Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ 13:393-403
60. Helbig KJ, Lau DT, Semendric L, Harley HA, Beard MR (2005) Analysis of ISG expression in chronic hepatitis C identifies viperin as a potential antiviral effector. Hepatology 42:702-710
61. Helbig KJ, Ruszkiewicz A, Lanford RE, Berzsenyi MD, Harley HA, McColl SR, Beard MR (2009) Differential expression of the CXCR3 ligands in chronic hepatitis C virus (HCV) infection and their modulation by HCV in vitro. J Virol 83:836-846
62. Helbig KJ, Eyre NS, Yip E, Narayana S, Li K, Fiches G, McCartney EM, Jangra RK, Lemon SM, Beard MR (2011) The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A. Hepatology 54:1506-1517
63. Hinson ER, Cresswell P (2009) The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proc Natl Acad Sci USA 106:20452-20457
64. Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, Sakai Y, Nakamura M, Shirasaki T, Horimoto K, Tanaka Y, Tokunaga K, Mizokami M, Kaneko S (2010) Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 139:499-509
65. Horner SM, Liu HM, Park HS, Briley J, Gale M Jr (2011) Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci USA 108:14590-14595
66. Horsmans Y, Berg T, Desager JP, Mueller T, Schott E, Fletcher SP, Steffy KR, Bauman LA, Kerr BM, Averett DR (2005) Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Hepatology 42:724-731
67. Itsui Y, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Koyama T, Takeda Y, Nakagawa M, Kakinuma S, Sekine Y, Maekawa S, Enomoto N, Watanabe M (2006) Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication. J Viral Hepat 13:690-700
68. Itsui Y, Sakamoto N, Kakinuma S, Nakagawa M, Sekine-Osajima Y, Tasaka-Fujita M, Nishimura-Sakurai Y, Suda G, Karakama Y, Mishima K, Yamamoto M, Watanabe T, Ueyama M, Funaoka Y, Azuma S, Watanabe M (2009) Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein. Hepatology 50:1727-1737
69. Jiang D, Guo H, Xu C, Chang J, Gu B, Wang L, Block TM, Guo JT (2008) Identification of three interferon-inducible cellular enzymes that inhibit the replication of hepatitis C virus. J Virol 82:1665-1678
70. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309:1577-1581
71. Jouan L, Melancon P, Rodrigue-Gervais IG, Raymond VA, Selliah S, Boucher G, Bilodeau M, Grandvaux N, Lamarre D (2010) Distinct antiviral signaling pathways in primary human hepatocytes and their differential disruption by HCV NS3 protease. J Hepatol 52:167-175
72. Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K (2007) The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104:14050-14055
73. Kanazawa N, Kurosaki M, Sakamoto N, Enomoto N, Itsui Y, Yamashiro T, Tanabe Y, Maekawa S, Nakagawa M, Chen CH, Kakinuma S, Oshima S, Nakamura T, Kato T, Wakita T, Watanabe M (2004) Regulation of hepatitis C virus replication by interferon regulatory factor 1. J Virol 78:9713-9720
74. Kang JI, Kwon SN, Park SH, Kim YK, Choi SY, Kim JP, Ahn BY (2009) PKR protein kinase is activated by hepatitis C virus and inhibits viral replication through translational control. Virus Res 142:51-56
75. Kato T, Date T, Miyamoto M, Furusaka A, Tokushige K, Mizokami M, Wakita T (2003) Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon. Gastroenterology 125:1808-1817
76. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101-105
77. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S (2008) Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205:1601-1610
78. Kato H, Takahasi K, Fujita T (2011) RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunol Rev 243:91-98
79. Kaukinen P, Sillanpaa M, Kotenko S, Lin R, Hiscott J, Melen K, Julkunen I (2006) Hepatitis C virus NS2 and NS3/4A proteins are potent inhibitors of host cell cytokine/chemokine gene expression. Virol J 3:66
80. Kawai T, Akira S (2008) Toll-like receptor and RIG-I-like receptor signaling. Ann N Y Acad Sci 1143:1-20
81. Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34:637-650
82. Kawasaki T, Kawai T, Akira S (2011) Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol Rev 243:61-73
83. Ke PY, Chen SS (2011) Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest 121:37-56
84. Kelly C, Klenerman P, Barnes E (2011) Interferon lambdas: the next cytokine storm. Gut 60:1284-1293
85. Kim KA, Lin W, Tai AW, Shao RX, Weinberg E, De Sa Borges CB, Bhan AK, Zheng H, Kamegaya Y, Chung RT (2009) Hepatic SOCS3 expression is strongly associated with non-response to therapy and race in HCV and HCV/HIV infection. J Hepatol 50:705-711
86. Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone SM, Rice CM (1997) Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science 277:570-574
87. Lan KH, Lan KL, Lee WP, Sheu ML, Chen MY, Lee YL, Yen SH, Chang FY, Lee SD (2007) HCV NS5A inhibits interferon-alpha signaling through suppression of STAT1 phosphorylation in hepatocyte-derived cell lines. J Hepatol 46:759-767
88. Lanford RE, Guerra B, Bigger CB, Lee H, Chavez D, Brasky KM (2007) Lack of response to exogenous interferon-alpha in the liver of chimpanzees chronically infected with hepatitis C virus. Hepatology 46:999-1008
89. Lau DT, Fish PM, Sinha M, Owen DM, Lemon SM, Gale M Jr (2008) Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients. Hepatology 47:799-809
90. Lee J, Wu CC, Lee KJ, Chuang TH, Katakura K, Liu YT, Chan M, Tawatao R, Chung M, Shen C, Cottam HB, Lai MM, Raz E, Carson DA (2006) Activation of anti-hepatitis C virus responses via Toll-like receptor 7. Proc Natl Acad Sci USA 103:1828-1833
91. Lemon SM (2010) Induction and evasion of innate antiviral responses by hepatitis C virus. J Biol Chem 285:22741-22747
92. Lemon SM, Walker C, Alter MJ, Yi M (2007) Hepatitis C viruses. In: Knipe D, Howley P, Griffin DE, Martin MA, Lamb RA et al (eds) Fields' virology, 5th edn. Lippincott Williams and Wilkins, Philadelphia, pp 1253-1304
93. Lemon SM, McKeating JA, Pietschmann T, Frick DN, Glenn JS, Tellinghuisen TL, Symons J, Furman PA (2010) Development of novel therapies for hepatitis C. Antiviral Res 86:79-92
94. Li K, Chen Z, Kato N, Gale M Jr, Lemon SM (2005) Distinct poly(I-C) and virus-activated signaling pathways leading to interferon-beta production in hepatocytes. J Biol Chem 280:16739-16747
95. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC, Ikeda M, Ray SC, Gale M Jr, Lemon SM (2005) Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 102:2992-2997
96. Li K, Li NL, Wei D, Pfeffer SR, Fan M, Pfeffer LM (2012) Activation of chemokine and inflammatory cytokine response in HCV-infected hepatocytes depends on TLR3 sensing of HCV dsRNA intermediates. Hepatology 55:666-675
97. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ (2005) Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 102:17717-17722
98. Liang Y, Shilagard T, Xiao SY, Snyder N, Lau D, Cicalese L, Weiss H, Vargas G, Lemon SM (2009) Visualizing hepatitis C virus infections in human liver by two-photon microscopy. Gastroenterology 137:1448-1458
99. Lin W, Kim SS, Yeung E, Kamegaya Y, Blackard JT, Kim KA, Holtzman MJ, Chung RT (2006) Hepatitis C virus core protein blocks interferon signaling by interaction with the STAT1 SH2 domain. J Virol 80:9226-9235
100. Lindenbach BD, Rice CM (2005) Unravelling hepatitis C virus replication from genome to function. Nature 436:933-938
101. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM (2005) Complete replication of hepatitis C virus in cell culture. Science 309:623-626
102. Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 23:275-306
103. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R (1999) Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110-113
104. Loo YM, Gale M Jr (2011) Immune signaling by RIG-I-like receptors. Immunity 34:680-692
105. Loo YM, Owen DM, Li K, Erickson AK, Johnson CL, Fish PM, Carney DS, Wang T, Ishida H, Yoneyama M, Fujita T, Saito T, Lee WM, Hagedorn CH, Lau DT, Weinman SA, Lemon SM, Gale M Jr (2006) Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. Proc Natl Acad Sci USA 103:6001-6006
106. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, Garcia-Sastre A, Katze MG, Gale M Jr (2008) Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol 82:335-345
107. Malakhova OA, Kim KI, Luo JK, Zou W, Kumar KG, Fuchs SY, Shuai K, Zhang DE (2006) UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J 25:2358-2367
108. Malathi K, Dong B, Gale M Jr, Silverman RH (2007) Small self-RNA generated by RNase L amplifies antiviral innate immunity. Nature 448:816-819
109. Marcello T, Grakoui A, Barba-Spaeth G, Machlin ES, Kotenko SV, MacDonald MR, Rice CM (2006) Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 131:1887-1898
110. Martell M, Esteban JI, Quer J, Genesca J, Weiner A, Esteban R, Guardia J, Gomez J (1992) Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution. J Virol 66:3225-3229
111. Marukian S, Jones CT, Andrus L, Evans MJ, Ritola KD, Charles ED, Rice CM, Dustin LB (2008) Cell culture-produced hepatitis C virus does not infect peripheral blood mononuclear cells. Hepatology 48:1843-1850
112. Marukian S, Andrus L, Sheahan TP, Jones CT, Charles ED, Ploss A, Rice CM, Dustin LB (2011) Hepatitis C virus induces interferon-lambda and interferon-stimulated genes in primary liver cultures. Hepatology 54:1913-1923
113. Matsumoto M, Oshiumi H, Seya T (2011) Antiviral responses induced by the TLR3 pathway. Rev Med Virol 21:67-77
114. Mattijssen S, Pruijn GJ (2012) Viperin, a key player in the antiviral response. Microbes Infect 14:419-426
115. Melen K, Fagerlund R, Nyqvist M, Keskinen P, Julkunen I (2004) Expression of hepatitis C virus core protein inhibits interferon-induced nuclear import of STATs. J Med Virol 73:536-547
116. Mengshol JA, Golden-Mason L, Rosen HR (2007) Mechanisms of disease: HCV-induced liver injury. Nat Clin Pract Gastroenterol Hepatol 4:622-634
117. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167-1172
118. Moradpour D, Penin F, Rice CM (2007) Replication of hepatitis C virus. Nat Rev Microbiol 5:453-463
119. Nguyen LH, Espert L, Mechti N, Wilson DM 3rd (2001) The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry 40:7174-7179
120. Onoguchi K, Yoneyama M, Takemura A, Akira S, Taniguchi T, Namiki H, Fujita T (2007) Viral infections activate types I and III interferon genes through a common mechanism. J Biol Chem 282:7576-7581
121. Oshiumi H, Okamoto M, Fujii K, Kawanishi T, Matsumoto M, Koike S, Seya T (2011) The TLR3/TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection. J Immunol 187:5320-5327
122. Osterlund PI, Pietila TE, Veckman V, Kotenko SV, Julkunen I (2007) IFN regulatory factor family members differentially regulate the expression of type III IFN (IFN-lambda) genes. J Immunol 179:3434-3442
123. Otsuka M, Kato N, Moriyama M, Taniguchi H, Wang Y, Dharel N, Kawabe T, Omata M (2005) Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses. Hepatology 41:1004-1012
124. Pavio N, Taylor DR, Lai MM (2002) Detection of a novel unglycosylated form of hepatitis C virus E2 envelope protein that is located in the cytosol and interacts with PKR. J Virol 76:1265-1272
125. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919-922
126. Pietschmann T, Zayas M, Meuleman P, Long G, Appel N, Koutsoudakis G, Kallis S, Leroux-Roels G, Lohmann V, Bartenschlager R (2009) Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations. PLoS Pathog 5:e1000475
127. Pindel A, Sadler A (2011) The role of protein kinase R in the interferon response. J Interferon Cytokine Res 31:59-70
128. Polyak SJ, Khabar KS, Paschal DM, Ezelle HJ, Duverlie G, Barber GN, Levy DE, Mukaida N, Gretch DR (2001) Hepatitis C virus nonstructural 5A protein induces interleukin-8, leading to partial inhibition of the interferon-induced antiviral response. J Virol 75:6095-6106
129. Polyak SJ, Khabar KS, Rezeiq M, Gretch DR (2001) Elevated levels of interleukin-8 in serum are associated with hepatitis C virus infection and resistance to interferon therapy. J Virol 75:6209-6211
130. Preiss S, Thompson A, Chen X, Rodgers S, Markovska V, Desmond P, Visvanathan K, Li K, Locarnini S, Revill P (2008) Characterization of the innate immune signalling pathways in hepatocyte cell lines. J Viral Hepat 15:888-900
131. Randall G, Chen L, Panis M, Fischer AK, Lindenbach BD, Sun J, Heathcote J, Rice CM, Edwards AM, McGilvray ID (2006) Silencing of USP18 potentiates the antiviral activity of interferon against hepatitis C virus infection. Gastroenterology 131:1584-1591
132. Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM (2007) Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci USA 104:12884-12889
133. Raychoudhuri A, Shrivastava S, Steele R, Kim H, Ray R, Ray RB (2011) ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. J Virol 85:12881-12889
134. Rehermann B (2009) Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J Clin Invest 119:1745-1754
135. Riordan SM, Skinner NA, Kurtovic J, Locarnini S, McIver CJ, Williams R, Visvanathan K (2006) Toll-like receptor expression in chronic hepatitis C: correlation with pro-inflammatory cytokine levels and liver injury. Inflamm Res 55:279-285
136. Robek MD, Boyd BS, Chisari FV (2005) Lambda interferon inhibits hepatitis B and C virus replication. J Virol 79:3851-3854
137. Rosen HR (2003) Hepatitis C pathogenesis: mechanisms of viral clearance and liver injury. Liver Transpl 9:S35-S43
138. Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M Jr (2008) Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature 454:523-527
139. Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L, Filipowicz W, Heim MH (2008) Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad Sci USA 105:7034-7039
140. Sarasin-Filipowicz M, Wang X, Yan M, Duong FH, Poli V, Hilton DJ, Zhang DE, Heim MH (2009) Alpha interferon induces long-lasting refractoriness of JAK-STAT signaling in the mouse liver through induction of USP18/UBP43. Mol Cell Biol 29:4841-4851
141. Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O (2010) LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci USA 107:1512-1517
142. Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM (2011) A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 472:481-485
143. Schulz O, Pichlmair A, Rehwinkel J, Rogers NC, Scheuner D, Kato H, Takeuchi O, Akira S, Kaufman RJ, Reis e Sousa C (2010) Protein kinase R contributes to immunity against specific viruses by regulating interferon mRNA integrity. Cell Host Microbe 7:354-361
144. Seki E, Brenner DA (2008) Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 48:322-335
145. Sen GC (2001) Viruses and interferons. Annu Rev Microbiol 55:255-281
146. Servant MJ, Tenoever B, Lin R (2002) Overlapping and distinct mechanisms regulating IRF-3 and IRF-7 function. J Interferon Cytokine Res 22:49-58
147. Seth RB, Sun L, Ea CK, Chen ZJ (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF3. Cell 122:669-682
148. Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ, Lemon SM (2012) Stabilization of hepatitis C RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci U S A 109:941-946
149. Shimoike T, McKenna SA, Lindhout DA, Puglisi JD (2009) Translational insensitivity to potent activation of PKR by HCV IRES RNA. Antiviral Res 83:228-237
150. Silverman RH (2007) Viral encounters with 2′,5′- oligoadenylate synthetase and RNase L during the interferon antiviral response. J Virol 81:12720-12729
151. Sir D, Chen WL, Choi J, Wakita T, Yen TS, Ou JH (2008) Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology 48:1054-1061
152. Siren J, Pirhonen J, Julkunen I, Matikainen S (2005) IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J Immunol 174:1932-1937
153. Smith KR, Suppiah V, O'Connor K, Berg T, Weltman M, Abate ML, Spengler U, Bassendine M, Matthews G, Irving WL, Powell E, Riordan S, Ahlenstiel G, Stewart GJ, Bahlo M, George J, Booth DR (2011) Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort. Genome Med 3:57
154. Stiffler JD, Nguyen M, Sohn JA, Liu C, Kaplan D, Seeger C (2009) Focal distribution of hepatitis C virus RNA in infected livers. PLoS One 4:e6661
155. Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, Wieland S, Bukh J, Purcell RH, Schultz PG, Chisari FV (2002) Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci USA 99:15669-15674
156. Sumpter R Jr, Loo YM, Foy E, Li K, Yoneyama M, Fujita T, Lemon SM, Gale M Jr (2005) Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J Virol 79:2689-2699
157. Syed GH, Amako Y, Siddiqui A (2010) Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol Metab 21:33-40
158. Taguchi T, Nagano-Fujii M, Akutsu M, Kadoya H, Ohgimoto S, Ishido S, Hotta H (2004) 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. J Gen Virol 85:959-969
159. Takahashi K, Asabe S, Wieland S, Garaigorta U, Gastaminza P, Isogawa M, Chisari FV (2010) Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection. Proc Natl Acad Sci USA 107:7431-7436
160. Tamura T, Yanai H, Savitsky D, Taniguchi T (2008) The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol 26:535-584
161. Tanida I, Fukasawa M, Ueno T, Kominami E, Wakita T, Hanada K (2009) Knockdown of autophagy-related gene decreases the production of infectious hepatitis C virus particles. Autophagy 5:937-945
162. Targett-Adams P, Boulant S, McLauchlan J (2008) Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J Virol 82:2182-2195
163. Tasaka M, Sakamoto N, Itakura Y, Nakagawa M, Itsui Y, Sekine-Osajima Y, Nishimura-Sakurai Y, Chen CH, Yoneyama M, Fujita T, Wakita T, Maekawa S, Enomoto N, Watanabe M (2007) Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response. J Gen Virol 88:3323-3333
164. Taura M, Eguma A, Suico MA, Shuto T, Koga T, Komatsu K, Komune T, Sato T, Saya H, Li JD, Kai H (2008) p53 regulates Toll-like receptor 3 expression and function in human epithelial cell lines. Mol Cell Biol 28:6557-6567
165. Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM (1999) Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285:107-110
166. Taylor DR, Puig M, Darnell ME, Mihalik K, Feinstone SM (2005) New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1. J Virol 79:6291-6298
167. Urban TJ, Thompson AJ, Bradrick SS, Fellay J, Schuppan D, Cronin KD, Hong L, McKenzie A, Patel K, Shianna KV, McHutchison JG, Goldstein DB, Afdhal N (2010) IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52:1888-1896
168. Uze G, Monneron D (2007) IL-28 and IL-29: newcomers to the interferon family. Biochimie 89:729-734
169. Uzri D, Gehrke L (2009) Nucleotide sequences and modifications that determine RIG-I/RNA binding and signaling activities. J Virol 83:4174-4184
170. Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber GN (2007) Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol 178:6444-6455
171. Vestal DJ, Jeyaratnam JA (2011) The guanylate-binding proteins: emerging insights into the biochemical properties and functions of this family of large interferon-induced guanosine triphosphatase. J Interferon Cytokine Res 31:89-97
172. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M, Zhao Z, Murthy K, Habermann A, Krausslich HG, Mizokami M, Bartenschlager R, Liang TJ (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11:791-796
173. Wald O, Weiss ID, Galun E, Peled A (2007) Chemokines in hepatitis C virus infection: pathogenesis, prognosis and therapeutics. Cytokine 39:50-62
174. Wang C, Pflugheber J, Sumpter R Jr, Sodora DL, Hui D, Sen GC, Gale M Jr (2003) Alpha interferon induces distinct translational control programs to suppress hepatitis C virus RNA replication. J Virol 77:3898-3912
175. Wang N, Liang Y, Devaraj S, Wang J, Lemon SM, Li K (2009) Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells. J Virol 83:9824-9834
176. Wang S, Wu X, Pan T, Song W, Wang Y, Zhang F, Yuan Z (2012) Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33. J Gen Virol 93:83-92
177. Weber F, Wagner V, Rasmussen SB, Hartmann R, Paludan SR (2006) Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol 80:5059-5064
178. Yang Y, Liang Y, Qu L, Chen Z, Yi M, Li K, Lemon SM (2007) Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor. Proc Natl Acad Sci USA 104:7253-7258
179. Yao L, Dong H, Zhu H, Nelson D, Liu C, Lambiase L, Li X (2011) Identification of the IFITM3 gene as an inhibitor of hepatitis C viral translation in a stable STAT1 cell line. J Viral Hepat 18:e523-e529
180. Yi M, Villanueva RA, Thomas DL, Wakita T, Lemon SM (2006) Production of infectious genotype 1a hepatitis C virus (Hutchinson strain) in cultured human hepatoma cells. Proc Natl Acad Sci USA 103:2310-2315
181. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T (2005) Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 175:2851-2858
182. Zeremski M, Petrovic LM, Talal AH (2007) The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J Viral Hepat 14:675-687
183. Zhang YL, Guo YJ, Bin L, Sun SH (2009) Hepatitis C virus single-stranded RNA induces innate immunity via Toll-like receptor 7. J Hepatol 51:29-38
184. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T, Burton DR, Wieland SF, Uprichard SL, Wakita T, Chisari FV (2005) Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci USA 102:9294-9299
185. Zhou Z, Wang N, Woodson SE, Dong Q, Wang J, Liang Y, Rijnbrand R, Wei L, Nichols JE, Guo JT, Holbrook MR, Lemon SM, Li K (2011) Antiviral activities of ISG20 in positive-strand RNA virus infections. Virology 409:175-188
186. Zhu H, Liu C (2003) Interleukin-1 inhibits hepatitis C virus subgenomic RNA replication by activation of extracellular regulated kinase pathway. J Virol 77:5493-5498
187. Zhu H, Butera M, Nelson DR, Liu C (2005) Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication. Virol J 2:80