Host genetics in immune-mediated hepatitis C virus clearance

Biomarkers in Medicine

Volumn 5, Issue 2, 2011, Pages 155-169

  Schmidt, Julia ^a   Thimme, Robert ^a   Neumann Haefelin, Christoph ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

hepatitis C virus; human leukocyte allele; IFN ; IL 28B; killer immunoglobulin like receptor; T cell response; viral clearance; viral persistence

Indexed keywords

ANTIVIRUS AGENT; EPITOPE; GAMMA INTERFERON; HLA A3 ANTIGEN; HLA B27 ANTIGEN; HLA B57 ANTIGEN; INTERLEUKIN 28B; NATURAL KILLER CELL RECEPTOR; PEGINTERFERON; PEGYLATED INTERFERON ALPHA; PROTEINASE INHIBITOR; RIBAVIRIN; UNCLASSIFIED DRUG; VIRUS ANTIGEN;

ALLELE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; GENE EXPRESSION; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HEREDITY; HOMOZYGOSITY; HUMAN; IL 28B GENE; IMMUNE RESPONSE; OUTCOME ASSESSMENT; REVIEW; VACCINATION; VIRAL CLEARANCE; VIRUS GENE; VIRUS IMMUNITY;

ALLELES; HEPACIVIRUS; HEPATITIS C; HISTOCOMPATIBILITY ANTIGENS CLASS I; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE SYSTEM;

HEPATITIS C VIRUS;

EID: 79953858550     PISSN: 17520363     EISSN: None     Source Type: Journal    
DOI: 10.2217/bmm.11.19     Document Type: Review

References (128)

1. Moradpour D, Brass V, Gosert R, Wolk B, Blum HE: Hepatitis C: Molecular virology and antiviral targets. Trends Mol. Med. 8(10), 476-482 (2002).
2. Lauer GM, Walker BD: Hepatitis C virus infection. N. Engl. J. Med. 345(1), 41-52 (2001). (Pubitemid 32634271)
3. Kronenberger B, Zeuzem S: Current and future treatment options for HCV. Ann. Hepatol. 8(2), 103-112 (2009).
4. Dustin LB, Rice CM: Flying under the radar: the immunobiology of hepatitis C Annu. Rev. Immunol. 25, 71-99 (2007). (Pubitemid 46697903)
5. Rehermann B: Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119(7), 1745-1754 (2009).
6. Walker CM: Adaptive immunity to the hepatitis C virus. Adv. Virus Res. 78, 43-86 (2010).
7. Horner SM, Gale M Jr: Intracellular innate immune cascades and interferon defenses that control hepatitis C virus. J. Interferon Cytokine Res. 29(9), 489-498 (2009).
8. Szabo G, Dolganiuc A: Hepatitis C and innate immunity: recent advances. Clin. Liver Dis. 12(3), 675-692 (2008). (Pubitemid 351952475)
9. Cheent K, Khakoo SI: Natural killer cells and hepatitis C: action and reaction. Gut 60(2), 268-278 (2010).
10. Diepolder HM, Zachoval R, Hoffmann RM et al.: Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346(8981), 1006-1007 (1995).
11. + T-cell response in acute hepatitis C. Gastroenterology 117(4), 933-941 (1999). (Pubitemid 29468237)
12. Lechner F, Wong DK, Dunbar PR et al.: Analysis of successful immune responses in persons infected with hepatitis C virus. J. Exp. Med. 191(9), 1499-1512 (2000). (Pubitemid 30257347)
13. Thimme R, Bukh J, Spangenberg HC et al.: Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease. Proc Natl Acad. Sci. USA 99 (24), 15661-15668 (2002). (Pubitemid 35403988)
14. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV: Determinants of viral clearance and persistence during acute hepatitis C virus infection. J. Exp. Med. 194(10), 1395-1406 (2001). (Pubitemid 33081515)
15. + T cells are required for protection from persistent hepatitis C virus infection. J. Exp. Med. 197(12), 1645-1655 (2003). (Pubitemid 36745340)
16. Grakoui A, Shoukry NH, Woollard DJ et al.: HCV persistence and immune evasion in the absence of memory T cell help. Science 302(5645), 659-662 (2003). (Pubitemid 37310924)
17. Pestka JM, Zeisel MB, Blaser E et al.: Rapid induction of virus-neutralizing antibodies and viral clearance in a single-source outbreak of hepatitis C. Proc Natl Acad. Sci. USA 104(14), 6025-6030 (2007). (Pubitemid 47175652)
18. Christie JM, Healey CJ, Watson J et al.: Clinical outcome of hypogammaglobulinaemic patients following outbreak of acute hepatitis C: 2 year follow up. Clin. Exp. Immunol. 110(1), 4-8 (1997). (Pubitemid 27428507)
19. Post JJ, Pan Y, Freeman AJ et al.: Clearance of hepatitis C viremia associated with cellular immunity in the absence of seroconversion in the hepatitis C incidence and transmission in prisons study cohort. J. Infect. Dis. 189(10), 1846-1855 (2004). (Pubitemid 38657221)
20. + T cell failure in hepatitis C virus infection. World J. Gastroenterol. 13(36), 4839-4847 (2007). (Pubitemid 47496749)
21. + T cells is linked to antigen recognition and T cell differentiation. PLoS Pathog. 6(6), e1000947 (2010).
22. Radziewicz H, Ibegbu CC, Fernandez ML et al.: Liver-infltrating 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(6), 2545-2553 (2007). (Pubitemid 46447020)
23. Urbani S, Amadei B, Tola D et al.: PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specifc CD8 exhaustion. J. Virol. 80(22), 11398-11403 (2006). (Pubitemid 44706581)
24. Alatrakchi N, Koziel M: Regulatory T cells and viral liver disease. J. Viral Hepat. 16(4), 223-229 (2009).
25. + T cells during chronic hepatitis C virus infection. J. Virol. 79(12), 7860-7867 (2005). (Pubitemid 40756821)
26. + regulatory T lymphocytes in hepatitis C virus infection. Hepatology 40(5), 1062-1071 (2004). (Pubitemid 39425561)
27. + T cell immunity: HCV evolution, from chimpanzees to man. J. Exp. Med. 201(11), 1709-1714 (2005). (Pubitemid 41002889)
28. Cox AL, Mosbruger T, Mao Q et al.: Cellular immune selection with hepatitis C virus persistence in humans. J. Exp. Med. 201(11), 1741-1752 (2005). (Pubitemid 41002893)
29. + T-cell failure in chronic hepatitis C virus infection. Hepatology 47(6), 1824-1836 (2008). (Pubitemid 351945550)
30. Timm J, Lauer GM, Kavanagh DG et al.: CD8 epitope escape and reversion in acute HCV infection. J. Exp. Med. 200(12), 1593-1604 (2004). (Pubitemid 40094183)
31. Rauch A, Gaudieri S, Thio C, Bochud PY: Host genetic determinants of spontaneous hepatitis C clearance. Pharmacogenomics 10(11), 1819-1837 (2009).
32. McKiernan SM, Hagan R, Curry M et al.: Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source. Hepatology 40(1), 108-114 (2004). (Pubitemid 38877575)
33. Thio Cl, Gao X, Goedert Jj et al.: HLA-CW*04 and hepatitis C virus persistence. J. Virol. 76(10), 4792-4797 (2002).
34. Kuniholm MH, Kovacs A, Gao X et al.: Specifc human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 51(5), 1514-1522 (2010).
35. Kim AY, Kuntzen T, Timm J et al.: Spontaneous control of HCV is associated with expression of HLA-B*57 and preservation of targeted epitopes. Gastroenterology 140(2), 686-696 (2011).
36. Hraber P, Kuiken C, Yusim K: Evidence for human leukocyte antigen heterozygote advantage against hepatitis C virus infection. Hepatology 46(6), 1713-1721 (2007).
37. Goulder PJ, Watkins DI: Impact of MHC class I diversity on immune control of immunodefciency virus replication. Nat. Rev. Immunol. 8(8), 619-630 (2008).
38. + T-cell epitope. Hepatology 51(1), 54-62 (2010).
39. Chuang WC, Sarkodie F, Brown CJ et al.: Protective effect of HLA-B57 on HCV genotype 2 infection in a West African population. J. Med. Virol. 79, 724-733 (2007). (Pubitemid 46709366)
40. + T-cell count in individuals coinfected with HIV-1. Blood 105(3), 1170-1178 (2005). (Pubitemid 40170890)
41. Lopez De Castro JA: HLA-B27 and the pathogenesis of spondyloarthropathies. Immunol. Lett. 108(1), 27-33 (2007).
42. + T cell response in mediating HCV clearance and evolution. Hepatology 43(3), 563-572 (2006).
43. Timm J, Li B, Daniels MG et al.: Human leukocyte antigen-associated sequence polymorphisms in hepatitis C virus reveal reproducible immune responses and constraints on viral evolution. Hepatology 46, 339-349 (2007). (Pubitemid 47344768)
44. Rauch A, James I, Pfafferott K et al.: Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen-restricted immune pressure. Hepatology 50(4), 1017-1029 (2009).
45. + T cells limit HCV escape from a protective HLA-B27-restricted human immune response. J. Clin. Invest. 119(2), 376-386 (2009).
46. Lauer GM, Barnes E, Lucas M et al.: High resolution ana lysis of cellular immune responses in resolved and persistent hepatitis C virus infection. Gastroenterology 127(3), 924-936 (2004). (Pubitemid 39208424)
47. Wong DK, Dudley DD, Afdhal NH et al.: Liver-derived CTL in hepatitis C virus infection: breadth and specifcity of responses in a cohort of persons with chronic infection. J. Immunol. 160(3), 1479-1488 (1998). (Pubitemid 28093451)
48. Merani S, Petrovic D, James I et al.: Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak. Hepatology 53(2), 396-405 (2011).
49. Simmonds P, Bukh J, Combet C et al.: Consensus proposals for a unifed system of nomenclature of hepatitis C virus genotypes. Hepatology 42(4), 962-973 (2005). (Pubitemid 41401136)
50. + T cells directed against NS3. Hepatology 50(3), 707-716 (2009).
51. Gaudieri S, Rauch A, Park LP et al.: Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection. J. Virol. 80(22), 11094-11104 (2006). (Pubitemid 44706550)
52. Lange CM, Roomp K, Dragan A et al.: HLA class I allele associations with HCV genetic variants in patients with chronic HCV genotypes 1a or 1b infection. J. Hepatol. 53(6), 1022-1028 (2010).
53. Itoh Y, Mizuki N, Shimada T et al.: High-throughput DNA typing of HLA-A,-B,-C, and-DRB1 loci by a PCR-SSOP-Luminex method in the Japanese population. Immunogenetics 57(10), 717-729 (2005). (Pubitemid 41598618)
54. Higashi Y, Kamikawaji N, Suko H, Ando M: Analysis of HLA alleles in Japanese patients with cirrhosis due to chronic hepatitis C J. Gastroenterol. Hepatol. 11(3), 241-246 (1996). (Pubitemid 26117823)
55. Kondo Y, Kobayashi K, Kobayashi T et al.: Distribution of the HLA class I allele in chronic hepatitis C and its association with serum ALT level in chronic hepatitis C Tohoku J. Exp. Med. 201(2), 109-117 (2003). (Pubitemid 37508999)
56. Mosaad YM, Farag RE, Arafa MM et al.: Association of human leucocyte antigen class I (HLA-A and HLA-B) with chronic hepatitis C virus infection in Egyptian patients. Scand. J. Immunol. 72(6), 548-553 (2010).
57. Kaplan DE, Sugimoto K, Newton K et al.: Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C Gastroenterology 132(2), 654-666 (2007). (Pubitemid 46274664)
58. Urbani S, Amadei B, Fisicaro P et al.: Outcome of acute hepatitis C is related to virus-specifc CD4 function and maturation of antiviral memory CD8 responses. Hepatology 44(1), 126-139 (2006). (Pubitemid 44049146)
59. Missale G, Bertoni R, Lamonaca V et al.: 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(3), 706-714 (1996). (Pubitemid 26349175)
60. Day CL, Seth NP, Lucas M et al.: Ex vivo ana lysis of human memory CD4 T cells specifc for hepatitis C virus using MHC class II tetramers. J. Clin. Invest. 112(6), 831-842 (2003). (Pubitemid 38063741)
61. Ulsenheimer A, Lucas M, Seth NP et al.: Transient immunological control during acute hepatitis C virus infection: ex vivo ana lysis of helper T-cell responses. J. Viral Hepat. 13(10), 708-714 (2006). (Pubitemid 44401200)
62. Singh R, Kaul R, Kaul A, Khan K: A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J. Gastroenterol. 13(12), 1770-1787 (2007). (Pubitemid 46706009)
63. Hong X, Yu RB, Sun NX, Wang B, Xu YC, Wu GL: Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-ana lysis. World J. Gastroenterol. 11(46), 7302-7307 (2005). (Pubitemid 43137680)
64. Yee LJ: Host genetic determinants in hepatitis C virus infection. Genes Immun. 5(4), 237-245 (2004). (Pubitemid 38967177)
65. Barrett S, Goh J, Coughlan B et al.: The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection. Gut 49(3), 423-430 (2001). (Pubitemid 32802579)
66. Barrett S, Ryan E, Crowe J: Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin. J. Hepatol. 30(6), 979-983 (1999). (Pubitemid 29278739)
67. Fanning LJ, Levis J, Kenny-Walsh E, Wynne F, Whelton M, Shanahan F: Viral clearance in hepatitis C (1b) infection: relationship with human leukocyte antigen class II in a homogeneous population. Hepatology 31 (6), 1334-1337 (2000). (Pubitemid 30351296)
68. McKiernan SM, Hagan R, Curry M et al.: The MHC is a major determinant of viral status, but not fbrotic stage, in individuals infected with hepatitis C Gastroenterology 118(6), 1124-1130 (2000). (Pubitemid 30346989)
69. Thio CL, Thomas DL, Goedert JJ et al.: Racial differences in HLA class II associations with hepatitis C virus outcomes. J. Infect. Dis. 184(1), 16-21 (2001). (Pubitemid 32568495)
70. Cramp ME, Carucci P, Underhill J, Naoumov NV, Williams R, Donaldson PT: Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia. J. Hepatol. 29(2), 207-213 (1998). (Pubitemid 28352805)
71. Lechmann M, Schneider EM, Giers G et al.: Increased frequency of the HLA-DR15 (B1*15011) allele in German patients with self-limited hepatitis C virus infection. Eur. J. Clin. Invest. 29(4), 337-343 (1999). (Pubitemid 29188827)
72. Harris RA, Sugimoto K, Kaplan DE, Ikeda F, Kamoun M, Chang KM: Human leukocyte antigen class II associations with hepatitis C virus clearance and virus-specifc CD4 T cell response among Caucasians and African-Americans. Hepatology 48(1), 70-79 (2008). (Pubitemid 351975532)
73. + T-cell epitopes within hepatitis C virus NS3 and NS4 proteins. J. Virol. 79(19), 12425-12433 (2005). (Pubitemid 41346105)
74. + T-helper-cell responses in resolved hepatitis C virus infection. J. Virol. 76(24), 12584-12595 (2002). (Pubitemid 35386944)
75. + T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection. J. Virol. 71(8), 6011-6019 (1997). (Pubitemid 27304939)
76. + T cells: implications for vaccine development. Hepatology 30(4), 1088-1098 (1999). (Pubitemid 29458301)
77. + Th cell response in spontaneously controlled hepatitis C virus infection includes dominant and highly promiscuous epitopes. J. Immunol. 175(6), 3603-3613 (2005). (Pubitemid 41292019)
78. + T cell responses against HCV: analysis of fuctuating dominant and subdominant HLA-DR11 restricted epitopes. J. Viral Hepat. 11(4), 324-331 (2004). (Pubitemid 38961877)
79. + T-cell determinants within the NS3 protein in subjects with spontaneously resolved HCV infection. Hepatology 37(3), 577-589 (2003). (Pubitemid 36258780)
80. Khakoo SI, Thio CL, Martin MP et al.: HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305(5685), 872-874 (2004). (Pubitemid 39038423)
81. Romero V, Azocar J, Zuniga J et al.: Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in hepatitis C virus infection outcome. Mol. Immunol. 45(9), 2429-2436 (2008).
82. Zuniga J, Romero V, Azocar J et al.: Protective KIR-HLA interactions for HCV infection in intravenous drug users. Mol. Immunol. 46(13), 2723-2727 (2009).
83. Rauch A, Laird R, Mckinnon E et al.: Infuence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolving hepatitis C virus infection. Tissue Antigens 69(Suppl. 1), 237-240 (2007). (Pubitemid 46625892)
84. Montes-Cano MA, Caro-Oleas JL, Romero-Gomez M et al.: HLA-C and KIR genes in hepatitis C virus infection. Hum. Immunol. 66(11), 1106-1109 (2005).
85. Knapp S, Warshow U, Hegazy D et al.: Consistent benefcial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus. Hepatology 51(4), 1168-1175 (2010).
86. Vidal-Castineira JR, Lopez-Vazquez A, Diaz-Pena R et al.: Effect of killer immunoglobulin-like receptors in the response to combined treatment in patients with chronic hepatitis C virus infection. J. Virol. 84(1), 475-481 (2010).
87. Ge D, Fellay J, Thompson AJ et al.: Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461(7262), 399-401 (2009).
88. Rauch A, Kutalik Z, Descombes P et al.: Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study Gastroenterology 138(4), 1338-1345, 1345. e1331-1345.e1337 (2010).
89. Suppiah V, Moldovan M, Ahlenstiel G et al.: IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy. Nat. Genet. 41(10), 1100-1104 (2009).
90. Tanaka Y, Nishida N, Sugiyama M et al.: Genome-wide association of IL28B with response to pegylated interferon-α and ribavirin therapy for chronic hepatitis C Nat. Genet. 41(10), 1105-1109 (2009).
91. McCarthy JJ, Li JH, Thompson A et al.: Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin. Gastroenterology 138(7), 2307-2314 (2010).
92. Rauch A, Rohrbach J, Bochud PY: The recent breakthroughs in the understanding of host genomics in hepatitis C Eur. J. Clin. Invest. 40(10), 950-959 (2010).
93. Montes-Cano MA, García-Lozano JR, Abad-Molina C et al.: Interleukin-28B genetic variants and hepatitis virus infection by different viral genotypes. Hepatology 52(1), 33-37 (2010).
94. Rallon NI, Naggie S, Benito JM et al.: Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 24(8), F23-F29 (2010).
95. Scherzer TM, Hofer H, Staettermayer AF et al.: Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon α-2a and ribavirin. J. Hepatol. (2011) (Epub ahead of print).
96. Sarrazin C, Susser S, Doehring A et al.: Importance of IL28B gene polymorphisms in hepatitis C virus genotype 2 and 3 infected patients. J. Hepatol. 54(3), 415-421 (2010).
97. Kawaoka T, Hayes CN, Ohishi W et al.: Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b. J. Hepatol. 54(3), 408-414 (2010).
98. Mangia A, Thompson AJ, Santoro R et al.: An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 139(3), 821-827 (2010).
99. Akuta N, Suzuki F, Hirakawa M et al.: Amino acid substitution in hepatitis C virus core region and genetic variation near the interleukin 28B gene predict viral response to telaprevir with peginterferon and ribavirin. Hepatology 52(2), 421-429 (2010).
100. Thomas DL, Thio CL, Martin MP et al.: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461(7265), 798-801 (2009).
101. Tillmann HL, Thompson AJ, Patel K et al.: A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology 139(5), 1586-1592 (2010).
102. Gerlach JT, Diepolder HM, Zachoval R et al.: Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology 125(1), 80-88 (2003). (Pubitemid 36799109)
103. Morrow MP, Pankhong P, Laddy DJ et al.: Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity. Blood 113(23), 5868-5877 (2009).
104. Morrow MP, Yan J, Pankhong P et al.: IL-28B/IFN-a;3 drives granzyme b loading and signifcantly increases CTL killing activity in macaques. Mol. Ther. 18(9), 1714-1723 (2010).
105. Morrow MP, Yan J, Pankhong P et al.: Unique Th1/Th2 phenotypes induced during priming and memory phases by use of interleukin-12 (IL-12) or IL-28B vaccine adjuvants in rhesus macaques. Clin. Vaccine Immunol. 17(10), 1493-1499 (2010).
106. Sommereyns C, Paul S, Staeheli P, Michiels T: IFN-α (IFN-α) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 4(3), e1000017 (2008).
107. Urban TJ, Thompson AJ, Bradrick SS et al.: IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology 52(6), 1888-1896 (2010).
108. Sarasin-Filipowicz M, Oakeley EJ, Duong FH et al.: Interferon signaling and treatment outcome in chronic hepatitis C. Proc Natl Acad. Sci. USA 105(19), 7034-7039 (2008). (Pubitemid 351754525)
109. Sarasin-Filipowicz M, Wang X, Yan M et al.: α-interferon induces long-lasting refractoriness of JAK-STAT signaling in the mouse liver through induction of USP18/UBP43. Mol. Cell Biol. 29(17), 4841-4851 (2009).
110. Salem ML, El-Demellawy M, El-Azm AR: The potential use of Toll-like receptor agonists to restore the dysfunctional immunity induced by hepatitis C virus. Cell Immunol. 262(2), 96-104 (2010).
111. Muir AJ, Shiffman ML, Zaman A et al.: Phase 1b study of pegylated interferon a;1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52(3), 822-832 (2010).
112. Thimme R, Neumann-Haefelin C, Boettler T, Blum HE: Adaptive immune responses to hepatitis C virus: from viral immunobiology to a vaccine. Biol. Chem. 389(5), 457-467 (2008). (Pubitemid 351874195)
113. Schott E, Witt H, Neumann K et al.: Association of TLR7 single nucleotide polymorphisms with chronic HCV-infection and response to interferon-α- based therapy J. Viral Hepat. 15(1), 71-78 (2008). (Pubitemid 350243584)
114. Knapp S, Yee LJ, Frodsham AJ et al.: Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Genes Immun. 4(6), 411-419 (2003). (Pubitemid 38967606)
115. Pandey JP, Astemborski J, Thomas DL: Epistatic effects of immunoglobulin GM and KM allotypes on outcome of infection with hepatitis C virus. J. Virol. 78(9), 4561-4565 (2004). (Pubitemid 38501076)
116. Pandey JP, Namboodiri AM, Luo Y et al.: Genetic markers of IgG infuence the outcome of infection with hepatitis C virus. J. Infect. Dis. 198(9), 1334-1336 (2008).
117. Knapp S, Hennig BJ, Frodsham AJ et al.: Interleukin-10 promoter polymorphisms and the outcome of hepatitis C virus infection. Immunogenetics 55(6), 362-369 (2003). (Pubitemid 37255487)
118. Lio D, Caruso C, Di Stefano R et al.: IL-10 and TNF-α polymorphisms and the recovery from HCV infection. Hum. Immunol. 64(7), 674-680 (2003). (Pubitemid 36828498)
119. Kimura T, Saito T, Yoshimura M et al.: Association of transforming growth factor-β1 functional polymorphisms with natural clearance of hepatitis C virus. J. Infect. Dis. 193(10), 1371-1374 (2006). (Pubitemid 43673384)
120. Wang JH, Zheng X, Ke X et al.: Ethnic and geographical differences in HLA associations with the outcome of hepatitis C virus infection. Virol. J. 6, 46 (2009).
121. Minton EJ, Smillie D, Neal KR, Irving WL, Underwood JC, James V: Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C virus Study Group. J. Infect. Dis. 178(1), 39-44 (1998). (Pubitemid 28328074)
122. Thursz M, Yallop R, Goldin R, Trepo C, Thomas HC: Infuence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 354(9196), 2119-2124 (1999). (Pubitemid 30008896)
123. Alric L, Fort M, Izopet J et al.: Genes of the major histocompatibility complex class II infuence the outcome of hepatitis C virus infection. Gastroenterology 113(5), 1675-1681 (1997). (Pubitemid 27461256)
124. Mangia A, Gentile R, Cascavilla I et al.: HLA class II favors clearance of HCV infection and progression of the chronic liver damage. J. Hepatol. 30(6), 984-989 (1999). (Pubitemid 29278740)
125. Zavaglia C, Martinetti M, Silini E et al.: Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C J. Hepatol. 28(1), 1-7 (1998). (Pubitemid 28122493)
126. Yenigun A, Durupinar B: Decreased frequency of the HLA-DRB1*11 allele in patients with chronic hepatitis C virus infection. J. Virol. 76(4), 1787-1789 (2002). (Pubitemid 34094626)
127. Tibbs C, Donaldson P, Underhill J, Thomson L, Manabe K, Williams R: Evidence that the HLA DQA1*03 allele confers protection from chronic HCV-infection in Northern European Caucasoids. Hepatology 24(6), 1342-1345 (1996). (Pubitemid 26399027)
128. Wawrzynowicz-Syczewska M, Underhill JA, Clare MA, Boron-Kaczmarska A, McFarlane IG, Donaldson PT: HLA class II genotypes associated with chronic hepatitis C virus infection and response to α-interferon treatment in Poland. Liver 20(3), 234-239 (2000). (Pubitemid 30342722)