Innate and adaptive immune responses in HCV infections

Journal of Hepatology

Volumn 61, Issue 1, 2014, Pages S14-S25

  Heim, Markus H ^a,b   Thimme, Robert ^c  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

^c UNIVERSITY OF FREIBURG   (Germany)

Author keywords

CD8+ T cells; Hepatitis C virus; Innate immunity; Interferon; Jak STAT; T cell exhaustion; Viral escape

Indexed keywords

PEGINTERFERON ALPHA; RIBAVIRIN; TOLL LIKE RECEPTOR 1; ANTIVIRUS AGENT; INTERFERON;

ADAPTIVE IMMUNITY; ARTICLE; CELL COMPARTMENTALIZATION; CHRONIC DISEASE; GENE EXPRESSION; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; INNATE IMMUNITY; LIVER; NATURAL KILLER CELL; SIGNAL TRANSDUCTION; T LYMPHOCYTE; TREATMENT RESPONSE; VIRUS REPLICATION; ANIMAL; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HEPACIVIRUS; IMMUNOLOGY; MOUSE; PATHOPHYSIOLOGY; PHYSIOLOGY;

ADAPTIVE IMMUNITY; ANIMALS; ANTIVIRAL AGENTS; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION, VIRAL; HEPACIVIRUS; HEPATITIS C; HUMANS; IMMUNITY, INNATE; INTERFERONS; MICE;

EID: 84913555946     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2014.06.035     Document Type: Review

References (156)

1. D. Lavanchy The global burden of hepatitis C Liver Int 29 2009 74 81
2. C.W. Shepard, L. Finelli, and M.J. Alter Global epidemiology of hepatitis C virus infection Lancet Infect Dis 5 2005 558 567
3. T. Santantonio, J. Wiegand, and J.T. Gerlach Acute hepatitis C: current status and remaining challenges J Hepatol 49 2008 625 633
4. G.M. Lauer, and B.D. Walker Hepatitis C virus infection N Engl J Med 345 2001 41 52
5. H.B. El-Serag Epidemiology of viral hepatitis and hepatocellular carcinoma Gastroenterology 142 2012 e1261
6. D.B. Stetson, and R. Medzhitov Type I interferons in host defence Immunity 25 2006 373 381
7. A. Iwasaki, and R. Medzhitov Toll-like receptor control of the adaptive immune responses Nat Immunol 5 2004 987 995
8. S. Akira, S. Uematsu, and O. Takeuchi Pathogen recognition and innate immunity Cell 124 2006 783 801
9. M. Yoneyama, and T. Fujita Function of RIG-I-like receptors in antiviral innate immunity J Biol Chem 282 2007 15315 15318
10. M. Yoneyama, M. Kikuchi, T. Natsukawa, N. Shinobu, T. Imaizumi, and M. Miyagishi The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses Nat Immunol 5 2004 730 737
11. T. Marcello, A. Grakoui, G. Barba-Spaeth, E.S. Machlin, S.V. Kotenko, and M.R. MacDonald Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics Gastroenterology 131 2006 1887 1898
12. S.D. Der, A. Zhou, B.R. Williams, and R.H. Silverman Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays Proc Natl Acad Sci U S A 95 1998 15623 15628
13. M.T. Dill, Z. Makowska, F.H. Duong, F. Merkofer, M. Filipowicz, and T.F. Baumert Interferon-gamma-stimulated genes, but not USP18, are expressed in livers of patients with acute hepatitis C Gastroenterology 143 2012 e776 776
14. M. Sarasin-Filipowicz, E.J. Oakeley, F.H. Duong, V. Christen, L. Terracciano, and W. Filipowicz Interferon signalling and treatment outcome in chronic hepatitis C Proc Natl Acad Sci U S A 105 2008 7034 7039
15. U. Muller, U. Steinhoff, L.F. Reis, S. Hemmi, J. Pavlovic, and R.M. Zinkernagel Functional role of type I and type II interferons in antiviral defence Science 264 1994 1918 1921
16. J.E. Durbin, R. Hackenmiller, M.C. Simon, and D.E. Levy Targeted disruption of the mouse Stat1 gene results in compromised innate immunity to viral disease Cell 84 1996 443 450
17. S. Dupuis, E. Jouanguy, S. Al-Hajjar, C. Fieschi, I.Z. Al-Mohsen, and S. Al-Jumaah Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency Nat Genet 33 2003 388 391
18. M. Mordstein, G. Kochs, L. Dumoutier, J.C. Renauld, S.R. Paludan, and K. Klucher Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses PLoS Pathog 4 2008 e1000151
19. M. Mordstein, E. Neugebauer, V. Ditt, B. Jessen, T. Rieger, and V. Falcone Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections J Virol 84 2010 5670 5677
20. S.V. Kotenko, G. Gallagher, V.V. Baurin, A. Lewis-Antes, M. Shen, and N.K. Shah IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex Nat Immunol 4 2003 69 77
21. R.P. Donnelly, F. Sheikh, S.V. Kotenko, and H. Dickensheets The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain J Leukoc Biol 76 2004 314 321
22. F.H. Duong, G. Trincucci, T. Boldanova, D. Calabrese, B. Campana, and I. Krol IFN-lambda receptor 1 expression is induced in chronic hepatitis C and correlates with the IFN-lambda3 genotype and with nonresponsiveness to IFN-alpha therapies J Exp Med 211 2014 857 868
23. J.E. Darnell Jr. STATs and gene regulation Science 277 1997 1630 1635
24. M.H. Heim, I.M. Kerr, G.R. Stark, and J.E. Darnell Jr. Contribution of STAT SH2 groups to specific interferon signalling by the Jak-STAT pathway Science 267 1995 1347 1349
25. J.E. Darnell Jr., I.M. Kerr, and G.R. Stark Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signalling proteins Science 264 1994 1415 1421
26. Z. Zhou, O.J. Hamming, N. Ank, S.R. Paludan, A.L. Nielsen, and R. Hartmann Type III interferon (IFN) induces a type I IFN-like response in a restricted subset of cells through signalling pathways involving both the Jak-STAT pathway and the mitogen-activated protein kinases J Virol 81 2007 7749 7758
27. D.L. Krebs, and D.J. Hilton SOCS proteins: negative regulators of cytokine signalling Stem Cells 19 2001 378 387
28. J.E. Fenner, R. Starr, A.L. Cornish, J.G. Zhang, D. Metcalf, and R.D. Schreiber Suppressor of cytokine signalling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity Nat Immunol 7 2006 33 39
29. W.S. Alexander, R. Starr, J.E. Fenner, C.L. Scott, E. Handman, and N.S. Sprigg SOCS1 is a critical inhibitor of interferon gamma signalling and prevents the potentially fatal neonatal actions of this cytokine Cell 98 1999 597 608
30. O.A. Malakhova, K.I. Kim, J.K. Luo, W. Zou, K.G. Kumar, and S.Y. Fuchs UBP43 is a novel regulator of interferon signalling independent of its ISG15 isopeptidase activity EMBO J 25 2006 2358 2367
31. M. Sarasin-Filipowicz, X. Wang, M. Yan, F.H. Duong, V. Poli, and D.J. Hilton Alpha interferon induces long-lasting refractoriness of JAK-STAT signalling in the mouse liver through induction of USP18/UBP43 Mol Cell Biol 29 2009 4841 4851
32. Z. Makowska, F.H. Duong, G. Trincucci, D.F. Tough, and M.H. Heim Interferon-beta and interferon-lambda signalling is not affected by interferon-induced refractoriness to interferon-alpha in vivo Hepatology 53 2011 1154 1163
33. R. Thimme, D. Oldach, K.M. Chang, C. Steiger, S.C. Ray, and F.V. Chisari Determinants of viral clearance and persistence during acute hepatitis C virus infection J Exp Med 194 2001 1395 1406
34. C.B. Bigger, K.M. Brasky, and R.E. Lanford DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection J Virol 75 2001 7059 7066
35. A.I. Su, J.P. Pezacki, L. Wodicka, A.D. Brideau, L. Supekova, and R. Thimme Genomic analysis of the host response to hepatitis C virus infection Proc Natl Acad Sci U S A 99 2002 15669 15674
36. M.E. Major, H. Dahari, K. Mihalik, M. Puig, C.M. Rice, and A.U. Neumann Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees Hepatology 39 2004 1709 1720
37. H. Dahari, M. Major, X. Zhang, K. Mihalik, C.M. Rice, and A.S. Perelson Mathematical modeling of primary hepatitis C infection: noncytolytic clearance and early blockage of virion production Gastroenterology 128 2005 1056 1066
38. R. Thimme, J. Bukh, H.C. Spangenberg, S. Wieland, J. Pemberton, and C. Steiger Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease Proc Natl Acad Sci U S A 99 2002 15661 15668
39. S. Marukian, L. Andrus, T.P. Sheahan, C.T. Jones, E.D. Charles, and A. Ploss Hepatitis C virus induces interferon-lambda and interferon-stimulated genes in primary liver cultures Hepatology 54 2011 1913 1923
40. E. Thomas, V.D. Gonzalez, Q. Li, A.A. Modi, W. Chen, and M. Noureddin HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons Gastroenterology 142 2012 978 988
41. H. Park, E. Serti, O. Eke, B. Muchmore, L. Prokunina-Olsson, and S. Capone IL-29 is the dominant type III interferon produced by hepatocytes during acute hepatitis C virus infection Hepatology 56 2012 2060 2070
42. K. Takahashi, S. Asabe, S. Wieland, U. Garaigorta, P. Gastaminza, and M. Isogawa Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, and inhibit infection Proc Natl Acad Sci U S A 107 2010 7431 7436
43. B. Langhans, B. Kupfer, I. Braunschweiger, S. Arndt, W. Schulte, and H.D. Nischalke Interferon-lambda serum levels in hepatitis C J Hepatol 54 2011 859 865
44. O. Bauhofer, A. Ruggieri, B. Schmid, P. Schirmacher, and R. Bartenschlager Persistence of HCV in quiescent hepatic cells under conditions of an interferon-induced antiviral response Gastroenterology 143 2012 e428
45. Z. Tian, Y. Chen, and B. Gao Natural killer cells in liver disease Hepatology 57 2013 1654 1662
46. B. Rehermann Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells Nat Med 19 2013 859 868
47. H.R. Rosen Emerging concepts in immunity to hepatitis C virus infection J Clin Invest 123 2013 4121 4130
48. S.I. Khakoo, C.L. Thio, M.P. Martin, C.R. Brooks, X. Gao, and J. Astemborski HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection Science 305 2004 872 874
49. C. Thoens, C. Berger, M. Trippler, H. Siemann, M. Lutterbeck, and R. Broering KIR2DL3NKG2A natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs J Hepatol 61 2014 475 481
50. B. Amadei, S. Urbani, A. Cazaly, P. Fisicaro, A. Zerbini, and P. Ahmed Activation of natural killer cells during acute infection with hepatitis C virus Gastroenterology 138 2010 1536 1545
51. N.H. Shoukry, S. Pelletier, and K.M. Chang A view to natural killer cells in hepatitis C Gastroenterology 141 2011 1144 1148
52. S. Pelletier, C. Drouin, N. Bedard, S.I. Khakoo, J. Bruneau, and N.H. Shoukry Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses J Hepatol 53 2010 805 816
53. J. Nattermann NK cells in acute hepatitis C J Hepatol 55 2011 265 267
54. J.M. Werner, T. Heller, A.M. Gordon, A. Sheets, A.H. Sherker, and E. Kessler Innate immune responses in hepatitis C virus exposed healthcare workers who do not develop acute infection Hepatology 58 2013 1621 1631
55. R. Thimme, M. Binder, and R. Bartenschlager Failure of innate and adaptive immune responses in controlling hepatitis C virus infection FEMS Microbiol Rev 36 2012 663 683
56. E.C. Shin, S.H. Park, M. Demino, M. Nascimbeni, K. Mihalik, and M. Major Delayed induction, not impaired recruitment, of specific CD8(+) T cells causes the late onset of acute hepatitis C Gastroenterology 141 2011 686 695 695 e681
57. P. Klenerman, and R. Thimme T cell responses in hepatitis C: the good, the bad and the unconventional Gut 61 2012 1226 1234
58. C. Logvinoff, M.E. Major, D. Oldach, S. Heyward, A. Talal, and P. Balfe Neutralizing antibody response during acute and chronic hepatitis C virus infection Proc Natl Acad Sci U S A 101 2004 10149 10154
59. J.M. Pestka, M.B. Zeisel, E. Blaser, P. Schurmann, B. Bartosch, and F.L. Cosset Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C Proc Natl Acad Sci U S A 104 2007 6025 6030
60. S. Cooper, A.L. Erickson, E.J. Adams, J. Kansopon, A.J. Weiner, and D.Y. Chien Analysis of a successful immune response against hepatitis C virus Immunity 10 1999 439 449
61. H.M. Diepolder, J.-T. Gerlach, R. Zachoval, R.M. Hoffmann, M.-C. Jung, and E.A. Wierenga Immunodominant CD4+ T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection J Virol 71 1997 6011 6019
62. F. Lechner, D.K. Wong, P.R. Dunbar, R. Chapman, R.T. Chung, and P. Dohrenwend Analysis of successful immune responses in persons infected with hepatitis C virus J Exp Med 191 2000 1499 1512
63. G. Missale, R. Bertoni, V. Lamonaca, A. Valli, M. Massari, and C. Mori Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response J Clin Invest 98 1996 706 714
64. A. Takaki, M. Wiese, G. Maertens, E. Depla, U. Seifert, and A. Liebetrau Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C Nat Med 6 2000 578 582
65. C. Neumann-Haefelin, and R. Thimme Adaptive immune responses in hepatitis C virus infection Curr Top Microbiol Immunol 369 2013 243 262
66. N.H. Shoukry, A. Grakoui, M. Houghton, D.Y. Chien, J. Ghrayeb, and K.A. Reimann Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection J Exp Med 197 2003 1645 1655
67. A. Grakoui, N.H. Shoukry, D.J. Woollard, J.H. Han, H.L. Hanson, and J. Ghrayeb HCV persistence and immune evasion in the absence of memory T cell help Science 302 2003 659 662
68. H. Kared, T. Fabre, N. Bedard, J. Bruneau, and N.H. Shoukry Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C PLoS Pathog 9 2013 e1003422
69. J. Jo, B. Bengsch, B. Seigel, S.J. Rau, J. Schmidt, and E. Bisse Low perforin expression of early differentiated HCV-specific CD8+ T cells limits their hepatotoxic potential J Hepatol 57 2012 9 16
70. S. Wieland, Z. Makowska, B. Campana, D. Calabrese, M.T. Dill, and J. Chung Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver Hepatology 59 2014 2121 2130
71. M.T. Dill, F.H. Duong, J.E. Vogt, S. Bibert, P.Y. Bochud, and L. Terracciano Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C Gastroenterology 140 2011 1021 1031
72. M. Honda, A. Sakai, T. Yamashita, Y. Nakamoto, E. Mizukoshi, and Y. Sakai Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C Gastroenterology 139 2010 499 509
73. T.J. Urban, A.J. Thompson, S.S. Bradrick, J. Fellay, D. Schuppan, and K.D. Cronin IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C Hepatology 52 2010 1888 1896
74. L. Prokunina-Olsson, B. Muchmore, W. Tang, R.M. Pfeiffer, H. Park, and H. Dickensheets A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus Nat Genet 45 2013 164 171
75. S. Bibert, T. Roger, T. Calandra, M. Bochud, A. Cerny, and N. Semmo IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction J Exp Med 210 2013 1109 1116
76. P. Bellecave, M. Sarasin-Filipowicz, O. Donze, A. Kennel, J. Gouttenoire, and E. Meylan Cleavage of mitochondrial antiviral signalling protein in the liver of patients with chronic hepatitis C correlates with a reduced activation of the endogenous interferon system Hepatology 51 2010 1127 1136
77. L. Chen, I. Borozan, J. Feld, J. Sun, L.L. Tannis, and C. Coltescu Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection Gastroenterology 128 2005 1437 1444
78. T. Asselah, I. Bieche, S. Narguet, A. Sabbagh, I. Laurendeau, and M.P. Ripault Liver gene expression signature to predict response to pegylated interferon plus ribavirin combination therapy in patients with chronic hepatitis C Gut 57 2008 516 524
79. U. Garaigorta, and F.V. Chisari Hepatitis C virus blocks interferon effector function by inducing protein kinase R phosphorylation Cell Host Microbe 6 2009 513 522
80. J.J. Feld, S. Nanda, Y. Huang, W. Chen, M. Cam, and S.N. Pusek Hepatic gene expression during treatment with peginterferon and ribavirin: identifying molecular pathways for treatment response Hepatology 46 2007 1548 1563
81. C.B. Bigger, B. Guerra, K.M. Brasky, G. Hubbard, M.R. Beard, and B.A. Luxon Intrahepatic gene expression during chronic hepatitis C virus infection in chimpanzees J Virol 78 2004 13779 13792
82. A. Amanzada, W. Kopp, U. Spengler, G. Ramadori, and S. Mihm Interferon-lambda4 (IFNL4) transcript expression in human liver tissue samples PLoS One 8 2013 e84026
83. D. Ge, J. Fellay, A.J. Thompson, J.S. Simon, K.V. Shianna, and T.J. Urban Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance Nature 461 2009 399 401
84. A. Rauch, Z. Kutalik, P. Descombes, T. Cai, J. Di Iulio, and T. Mueller Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study Gastroenterology 138 2010 1338 1345 1345 e1331-e1337
85. D.L. Thomas, C.L. Thio, M.P. Martin, Y. Qi, D. Ge, and C. O'Huigin Genetic variation in IL28B and spontaneous clearance of hepatitis C virus Nature 461 2009 798 801
86. Y. Tanaka, N. Nishida, M. Sugiyama, M. Kurosaki, K. Matsuura, and N. Sakamoto Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C Nat Genet 41 2009 1105 1109
87. V. Suppiah, M. Moldovan, G. Ahlenstiel, T. Berg, M. Weltman, and M.L. Abate IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy Nat Genet 41 2009 1100 1104
88. P.V. Aka, M.H. Kuniholm, R.M. Pfeiffer, A.S. Wang, W. Tang, and S. Chen Association of the IFNL4-deltag allele with impaired spontaneous clearance of hepatitis C virus J Infect Dis 209 2014 350 354
89. M. Honda, T. Shirasaki, T. Shimakami, A. Sakai, R. Horii, and K. Arai Hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis C patients with different interleukin-28B genotypes Hepatology 59 2014 828 838
90. H. Konishi, T. Motomura, Y. Matsumoto, N. Harimoto, T. Ikegami, and T. Yoshizumi Interferon-lambda4 genetic polymorphism is associated with the therapy response for hepatitis C virus recurrence after a living donor liver transplant J Viral Hepat 21 2014 397 404
91. HapMapConsortium A haplotype map of the human genome Nature 437 2005 1299 1320
92. J. Nattermann, G. Feldmann, G. Ahlenstiel, B. Langhans, T. Sauerbruch, and U. Spengler Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis C Gut 55 2006 869 877
93. M.U. Mondelli, S. Varchetta, and B. Oliviero Natural killer cells in viral hepatitis: facts and controversies Eur J Clin Invest 40 2010 851 863
94. B. Edlich, G. Ahlenstiel, A. Zabaleta Azpiroz, J. Stoltzfus, M. Noureddin, and E. Serti Early changes in interferon signalling define natural killer cell response and refractoriness to interferon-based therapy of hepatitis C patients Hepatology 55 2012 39 48
95. T. Miyagi, T. Takehara, K. Nishio, S. Shimizu, K. Kohga, and W. Li Altered interferon-alpha-signalling in natural killer cells from patients with chronic hepatitis C virus infection J Hepatol 53 2010 424 430
96. S. Lunemann, D.F. Malone, J. Hengst, K. Port, J. Grabowski, and K. Deterding Compromised function of natural killer cells in acute and chronic viral hepatitis J Infect Dis 209 2014 1362 1373
97. K.A. Holder, S.N. Stapleton, M.E. Gallant, R.S. Russell, and M.D. Grant Hepatitis C virus-infected cells downregulate NKp30 and inhibit ex vivo NK cell functions J Immunol 191 2013 3308 3318
98. G. Ahlenstiel, R.H. Titerence, C. Koh, B. Edlich, J.J. Feld, and Y. Rotman Natural killer cells are polarized toward cytotoxicity in chronic hepatitis C in an interferon-alfa-dependent manner Gastroenterology 138 2010 e321 322
99. B. Oliviero, S. Varchetta, E. Paudice, G. Michelone, M. Zaramella, and D. Mavilio Natural killer cell functional dichotomy in chronic hepatitis B and chronic hepatitis C virus infections Gastroenterology 137 2009 1151 1160 1160 e1151-e1157
100. K.A. Stegmann, N.K. Bjorkstrom, H. Veber, S. Ciesek, P. Riese, and J. Wiegand Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection Gastroenterology 138 2010 1885 1897
101. B. Kramer, C. Korner, M. Kebschull, A. Glassner, M. Eisenhardt, and H.D. Nischalke Natural killer p46High expression defines a natural killer cell subset that is potentially involved in control of hepatitis C virus replication and modulation of liver fibrosis Hepatology 56 2012 1201 1213
102. S. Zhang, B. Saha, K. Kodys, and G. Szabo IFN-gamma production by human natural killer cells in response to HCV-infected hepatoma cells is dependent on accessory cells J Hepatol 59 2013 442 449
103. D. Sene, F. Levasseur, M. Abel, M. Lambert, X. Camous, and C. Hernandez Hepatitis C virus (HCV) evades NKG2D-dependent NK cell responses through NS5A-mediated imbalance of inflammatory cytokines PLoS Pathog 6 2010 e1001184
104. J.C. Yoon, J.B. Lim, J.H. Park, and J.M. Lee Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells J Virol 85 2011 12557 12569
105. J.C. Yoon, M. Shiina, G. Ahlenstiel, and B. Rehermann Natural killer cell function is intact after direct exposure to infectious hepatitis C virions Hepatology 49 2009 12 21
106. H. Kim, S.K. Bose, K. Meyer, and R. Ray Hepatitis C virus impairs natural killer cell-mediated augmentation of complement synthesis J Virol 88 2014 2564 2571
107. L. Golden-Mason, K.M. Bambha, L. Cheng, C.D. Howell, M.W. Taylor, and P.J. Clark Natural killer inhibitory receptor expression associated with treatment failure and interleukin-28B genotype in patients with chronic hepatitis C Hepatology 54 2011 1559 1569
108. T. Pembroke, A. Christian, E. Jones, R.K. Hills, E.C. Wang, and A.M. Gallimore The paradox of NKp46+ natural killer cells: drivers of severe hepatitis C virus-induced pathology but in-vivo resistance to interferon alpha treatment Gut 63 2014 515 524
109. R. Thimme NKp46+ expression on NK cells as a biomarker for liver pathology and IFN-responsiveness in HCV infection Gut 63 2014 382 384
110. B. Oliviero, D. Mele, E. Degasperi, A. Aghemo, E. Cremonesi, and M.G. Rumi Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic HCV infection J Hepatol 59 2013 38 44
111. G. Ahlenstiel, B. Edlich, L.J. Hogdal, Y. Rotman, M. Noureddin, and J.J. Feld Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C Gastroenterology 141 2011 1231 1239 1239 e1231-e1232
112. T. von Hahn, J.C. Yoon, H. Alter, C.M. Rice, B. Rehermann, and P. Balfe Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo Gastroenterology 132 2007 667 678
113. E. Falkowska, F. Kajumo, E. Garcia, J. Reinus, and T. Dragic Hepatitis C virus envelope glycoprotein E2 glycans modulate entry, CD81 binding, and neutralization J Virol 81 2007 8072 8079
114. F. Helle, A. Goffard, V. Morel, G. Duverlie, J. McKeating, and Z.Y. Keck The neutralizing activity of anti-hepatitis C virus antibodies is modulated by specific glycans on the E2 envelope protein J Virol 81 2007 8101 8111
115. J.M. Timpe, Z. Stamataki, A. Jennings, K. Hu, M.J. Farquhar, and H.J. Harris Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies Hepatology 47 2008 17 24
116. C.L. Brimacombe, J. Grove, L.W. Meredith, K. Hu, A.J. Syder, and M.V. Flores Neutralizing antibody-resistant hepatitis C virus cell-to-cell transmission J Virol 85 2011 596 605
117. K.M. Chang, B. Rehermann, J.G. McHutchison, C. Pasquinelli, S. Southwood, and A. Sette Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus J Clin Invest 100 1997 2376 2385
118. A. Weiner, A.L. Erickson, J. Kansopon, K. Crawford, E. Muchmore, and A.L. Hughes Persistent hepatitis C virus infection in a chimpanzee is associated with emergence of a cytotoxic T lymphocyte escape variant Proc Natl Acad Sci U S A 92 1995 2755 2759
119. A.L. Erickson, M. Houghton, Q.L. Choo, A.J. Weiner, R. Ralston, and E. Muchmore Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C J Immunol 151 1993 4189 4199
120. A.L. Cox, T. Mosbruger, G.M. Lauer, D. Pardoll, D.L. Thomas, and S.C. Ray Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C Hepatology 42 2005 104 112
121. I. Tester, S. Smyk-Pearson, P. Wang, A. Wertheimer, E. Yao, and D.M. Lewinsohn Immune evasion vs. recovery after acute hepatitis C virus infection from a shared source J Exp Med 201 2005 1725 1731
122. J. Timm, G.M. Lauer, D.G. Kavanagh, I. Sheridan, A.Y. Kim, and M. Lucas CD8 epitope escape and reversion in acute HCV infection J Exp Med 200 2004 1593 1604
123. J.R. Honegger, S. Kim, A.A. Price, J.A. Kohout, K.L. McKnight, and M.R. Prasad Loss of immune escape mutations during persistent HCV infection in pregnancy enhances replication of vertically transmitted viruses Nat Med 19 2013 1529 1533
124. E. Dazert, C. Neumann-Haefelin, S. Bressanelli, K. Fitzmaurice, J. Kort, and J. Timm Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27-restricted human immune response J Clin Invest 119 2009 376 386
125. ∗03 allele in hepatitis C virus infection Gut 60 2011 1563 1571
126. M.J. Fuller, N.H. Shoukry, T. Gushima, D.G. Bowen, B. Callendret, and K.J. Campbell Selection-driven immune escape is not a significant factor in the failure of CD4 T cell responses in persistent hepatitis C virus infection Hepatology 51 2010 378 387
127. B. Rehermann Hepatitis C virus vs. innate and adaptive immune responses: a tale of coevolution and coexistence J Clin Invest 119 2009 1745 1754
128. H. Radziewicz, C.C. Ibegbu, M.L. Fernandez, K.A. Workowski, K. Obideen, and M. Wehbi Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression J Virol 81 2007 2545 2553
129. A. Penna, M. Pilli, A. Zerbini, A. Orlandini, S. Mezzadri, and L. Sacchelli Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection Hepatology 45 2007 588 601
130. N. Nakamoto, D.E. Kaplan, J. Coleclough, Y. Li, M.E. Valiga, and M. Kaminski Functional restoration of HCV-specific CD8 T cells by PD-1 blockade is defined by PD-1 expression and compartmentalization Gastroenterology 134 2008 1927 1937 1937 e1921-e1922
131. L. Golden-Mason, B. Palmer, J. Klarquist, J.A. Mengshol, N. Castelblanco, and H.R. Rosen Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific CD8+ T cells associated with reversible immune dysfunction J Virol 81 2007 9249 9258
132. H. Radziewicz, C.C. Ibegbu, H. Hon, M.K. Osborn, K. Obideen, and M. Wehbi Impaired hepatitis C virus (HCV)-specific effector CD8+ T cells undergo massive apoptosis in the peripheral blood during acute HCV infection and in the liver during the chronic phase of infection J Virol 82 2008 9808 9822
133. N. Nakamoto, H. Cho, A. Shaked, K. Olthoff, M.E. Valiga, and M. Kaminski Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade PLoS Pathog 5 2009 e1000313
134. R.H. McMahan, L. Golden-Mason, M.I. Nishimura, B.J. McMahon, M. Kemper, and T.M. Allen Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity J Clin Invest 120 2010 4546 4557
135. D.C. Kroy, D. Ciuffreda, J.H. Cooperrider, M. Tomlinson, G.D. Hauck, and J. Aneja Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors Gastroenterology 146 2014 550 561
136. V. Schlaphoff, S. Lunemann, P.V. Suneetha, J. Jaroszewicz, J. Grabowski, and J. Dietz Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+ T cells PLoS Pathog 7 2011 e1002045
137. B. Bengsch, B. Seigel, M. Ruhl, J. Timm, M. Kuntz, and H.E. Blum Coexpression of PD-1, 2B4, CD160, and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation PLoS Pathog 6 2010 e1000947
138. M.J. Fuller, B. Callendret, B. Zhu, G.J. Freeman, D.L. Hasselschwert, and W. Satterfield Immunotherapy of chronic hepatitis C virus infection with antibodies against programmed cell death-1 (PD-1) Proc Natl Acad Sci U S A 110 2013 15001 15006
139. D. Gardiner, J. Lalezari, E. Lawitz, M. Dimicco, R. Ghalib, and K.R. Reddy A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C virus infection PLoS One 8 2013 e63818
140. V. Kasprowicz, J. Schulze Zur Wiesch, T. Kuntzen, B.E. Nolan, S. Longworth, and A. Berical High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome J Virol 82 2008 3154 3160
141. E.C. Shin, S.H. Park, M. Nascimbeni, M. Major, L. Caggiari, and V. de Re The frequency of CD127(+) hepatitis C virus (HCV)-specific T cells but not the expression of exhaustion markers predicts the outcome of acute HCV infection J Virol 87 2013 4772 4777
142. N. Semmo, C.L. Day, S.M. Ward, M. Lucas, G. Harcourt, and A. Loughry Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection Hepatology 41 2005 1019 1028
143. T. Boettler, H.C. Spangenberg, C. Neumann-Haefelin, E. Panther, S. Urbani, and C. Ferrari T cells with a CD4+CD25+ regulatory phenotype suppress in vitro proliferation of virus-specific CD8+ T cells during chronic hepatitis C virus infection J Virol 79 2005 7860 7867
144. R. Cabrera, Z. Tu, Y. Xu, R.J. Firpi, H.R. Rosen, and C. Liu An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection Hepatology 40 2004 1062 1071
145. S.M. Rushbrook, S.M. Ward, E. Unitt, S.L. Vowler, M. Lucas, and P. Klenerman Regulatory T cells suppress in vitro proliferation of virus-specific CD8+ T cells during persistent hepatitis C virus infection J Virol 79 2005 7852 7859
146. S.M. Ward, B.C. Fox, P.J. Brown, J. Worthington, S.B. Fox, and R.W. Chapman Quantification and localisation of FOXP3+ T lymphocytes and relation to hepatic inflammation during chronic HCV infection J Hepatol 47 2007 316 324
147. D. Franceschini, M. Paroli, V. Francavilla, M. Videtta, S. Morrone, and G. Labbadia PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV J Clin Invest 119 2009 551 564
148. D. Accapezzato, V. Francavilla, M. Paroli, M. Casciaro, L.V. Chircu, and A. Cividini Hepatic expansion of a virus-specific regulatory CD8(+) T cell population in chronic hepatitis C virus infection J Clin Invest 113 2004 963 972
149. M. Abel, D. Sene, S. Pol, M. Bourliere, T. Poynard, and F. Charlotte Intrahepatic virus-specific IL-10-producing CD8 T cells prevent liver damage during chronic hepatitis C virus infection Hepatology 44 2006 1607 1616
150. G. Badr, N. Bedard, M.S. Abdel-Hakeem, L. Trautmann, B. Willems, and J.P. Villeneuve Early interferon therapy for hepatitis C virus infection rescues polyfunctional, long-lived CD8+ memory T cells J Virol 82 2008 10017 10031
151. M.S. Abdel-Hakeem, N. Bedard, G. Badr, M. Ostrowski, R.P. Sekaly, and J. Bruneau Comparison of immune restoration in early vs. late alpha interferon therapy against hepatitis C virus J Virol 84 2010 10429 10435
152. G. Missale, M. Pilli, A. Zerbini, A. Penna, L. Ravanetti, and V. Barili Lack of full CD8 functional restoration after antiviral treatment for acute and chronic hepatitis C virus infection Gut 61 2012 1076 1084
153. B. Seigel, B. Bengsch, V. Lohmann, R. Bartenschlager, H.E. Blum, and R. Thimme Factors that determine the antiviral efficacy of HCV-specific CD8(+) T cells ex vivo Gastroenterology 144 2013 426 436
154. B. Martin, N. Hennecke, V. Lohmann, A. Kayser, C. Neumann-Haefelin, and G. Kukolj Restoration of HCV-specific CD8+ T cell function by interferon-free therapy J Hepatol 61 3 2014 538 543 10.1016/j.jhep.2014.05.043
155. R.E. Lanford, E.S. Hildebrandt-Eriksen, A. Petri, R. Persson, M. Lindow, and M.E. Munk Therapeutic silencing of MicroRNA-122 in primates with chronic hepatitis C virus infection Science 327 2010 198 201
156. P.M. Odorizzi, and E.J. Wherry Immunology. An interferon paradox Science 340 2013 155 156