Understanding the molecular mechanism(s) of hepatitis C virus (HCV) induced interferon resistance

Infection, Genetics and Evolution

Volumn 19, Issue , 2013, Pages 113-119

  Qashqari, Hanadi ^a   Al Mars, Amany ^a   Chaudhary, Adeel ^a   Abuzenadah, Adel ^a   Damanhouri, Ghazi ^a   Alqahtani, Mohammed ^a   Mahmoud, Maged ^a   El Sayed Zaki, Maysaa ^b   Fatima, Kaneez ^c   Qadri, Ishtiaq ^a  

^a KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

^b MANSOURA UNIVERSITY   (Egypt)

^c IQ Institute of Infection and Immunity   (Pakistan)

Author keywords

Hepatitis C virus (HCV); Interferon (IFN); Interferon stimulatory genes (ISGs); Protein kinase R (PKR); Single nucleotide polymorphism (SNP); Suppressor of cell signaling (SOCS)

Indexed keywords

CORE PROTEIN; DOUBLE STRANDED RNA; GAMMA INTERFERON; INTERFERON; INTERFERON REGULATORY FACTOR 9; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 28; JANUS KINASE; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4; NONSTRUCTURAL PROTEIN 4A; NONSTRUCTURAL PROTEIN 5A; NONSTRUCTURAL PROTEIN 5B; PEGINTERFERON; PROTEIN KINASE R; RIBAVIRIN; STAT1 PROTEIN; STAT2 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING; SUPPRESSOR OF CYTOKINE SIGNALING 1; TOLL LIKE RECEPTOR 3; VIRUS PROTEIN;

ANTIVIRAL RESISTANCE; COMPLEX FORMATION; CONTROLLED STUDY; FATTY LIVER; GENE EXPRESSION; GENETIC POLYMORPHISM; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HEREDITY; HUMAN; INSULIN RESISTANCE; LIVER FIBROSIS; OBESITY; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; STEATOSIS; VIRUS REPLICATION;

BOC; BOCEPREVIR; CD; CLUSTER OF DIFFERENTIATION; DOUBLE STRANDED RNA VIRUSES; DSRNA; EIF2Α; ENDOPLASMIC RETICULUM; ER; EUKARYOTIC INITIATION FACTOR 2Α; GAMMA INTERFERON ACTIVATION SITE; GAS; GENOTYPE; GT; HCV; HEPATITIS C VIRUS; HEPATITIS C VIRUS (HCV); IFN; IFN-STIMULATED RESPONSE ELEMENTS; IFN-Α RECEPTOR; IFNAR; IL; INSULIN RESISTANCE; INTERFERON; INTERFERON (IFN); INTERFERON AND RIBAVIRIN RESISTANCE DETERMINING REGION; INTERFERON REGULATORY FACTOR 3; INTERFERON SENSITIVITY DETERMINING REGION; INTERFERON STIMULATORY GENES; INTERFERON STIMULATORY GENES (ISGS); INTERLEUKIN; INTERNAL RIBOSOME ENTRY SITE; IR; IRES; IRF3; IRRDR; ISDR; ISG; ISRE; NF-ΚB; NUCLEAR FACTOR KAPPA-LIGHT-CHAIN-ENHANCER OF ACTIVATED B CELLS; PEPHD; PHOSPHORYLATION HOMOLOGY DOMAIN; PI; PKR; PROTEASE INHIBITOR; PROTEIN KINASE R; PROTEIN KINASE R (PKR); RE-1; REPRESSOR ELEMENT-1; REPRESSOR ELEMENT-1 SILENCING TRANSCRIPTION FACTOR; REST; SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION; SINGLE NUCLEOTIDE POLYMORPHISM (SNP); SINGLE NUCLEOTIDE POLYMORPHISMS; SNP; SOCS; STAT; SUPPRESSOR OF CELL SIGNALING (SOCS); SUPPRESSOR OF CYTOKINE SIGNALING; SUSTAINED VIROLOGICAL RESPONSE; SVR; T-HELPER; TELAPREVIR; TH; TLR3; TOLL LIKE RECEPTOR 3; TVR; UNFOLDED PROTEIN RESPONSE; UNTRANSLATED REGIONS; UPR; UTR;

ANTIVIRAL AGENTS; DRUG RESISTANCE, VIRAL; GENOTYPE; HEPACIVIRUS; HEPATITIS C; HOST-PATHOGEN INTERACTIONS; HUMANS; INTERFERONS; VIRAL PROTEINS;

EID: 84880955471     PISSN: 15671348     EISSN: 15677257     Source Type: Journal    
DOI: 10.1016/j.meegid.2013.06.025     Document Type: Review

References (76)

1. Afzal S., Idrees M., Ali M., Ilyas M., Hussain A., Akram M., Butt S., Saleem S., Rehman I.U., Ali L., Shahid M. Envelope 2 protein phosphorylation sites S75 & 277 of hepatitis C virus genotype 1a and interferon resistance: a sequence alignment approach. Virol J. 2011, 15(8):71.
2. Akuta N., Suzuki F., Hirakawa M., Kawamura Y., Sezaki H., Suzuki Y., Hosaka T., Kobayashi M., Kobayashi M., Saitoh S., Arase Y., Ikeda K., Chayama K., Nakamura Y., Kumada H. Amino acid substitution in HCV core/NS5A region and genetic variation near IL28B gene affect treatment efficacy to interferon plus ribavirin combination therapy. Intervirology 2012, 55(3):231-241.
3. Asselah T., Estrabaud E., Bieche I., Lapalus M., De Muynck S., Vidaud M., Saadoun D., Soumelis V., Marcellin P. Hepatitis C: viral and host factors associated with non-response to pegylated interferon plus ribavirin. Liver Int. 2010, 30(9):1259-1269.
4. Asselah T., De Muynck S., Broët P., Masliah-Planchon J., Blanluet M., Bièche I., Lapalus M., Martinot-Peignoux M., Lada O., Estrabaud E., Zhang Q., El Ray A., Vidaud D., Ripault M.P., Boyer N., Bedossa P., Valla D., Vidaud M., Marcellin P. IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C. J. Hepatol. 2012, 56(3):527-532.
5. Bartenschlager R., Lohmann V. Replication of hepatitis C virus. J. Gen. Virol. 2000, 81(Pt 7):1631-1648.
6. Bellanti F., Vendemiale G., Altomare E., Serviddio G. The impact of interferon lambda 3 gene polymorphism on natural course and treatment of hepatitis C. Clin. Dev. Immunol. 2012, 849373:9.
7. Bellecave P., Sarasin-Filipowicz M., Donzé O., Kennel A., Gouttenoire J., Meylan E., Terracciano L., Tschopp J., Sarrazin C., Berg T., Moradpour D., Heim M.H. 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 2010, 51(4):1127-1136.
8. Bode J.G., Ludwig S., Ehrhardt C., Albrecht U., Erhardt A., Schaper F., Heinrich P.C., Häussinger D. IFN-α antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J. 2003, 17:488-490.
9. Bowden D.S., Berzsenyi M.D. Chronic hepatitis C virus infection: genotyping and its clinical role. Future Microbiol. 2006, 1(1):103-112.
10. Chayama K., Suzuki F., Tsubota A., Kobayashi M., Arase Y., Saitoh S., Suzuki Y., Murashima N., Ikeda K., Takahashi N., Kinoshita M., Kumada H. Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy. Hepatology 2000, 32(5):1138-1144.
11. Chen L., Borozan I., Feld J., Sun J., Tannis L.L., Coltescu C., Heathcote J., Edwards A.M., McGilvray I.D. Hepatic gene expression discriminates responders and nonresponders in treatment of chronic hepatitis C viral infection. Gastroenterology 2005, 128:1437-1444.
12. Chevaliez S., Pawlotsky J.M. HCV genome and life cycle. Hepatitis C Viruses: Genomes and Molecular Biology 2006, Horizon Bioscience, UK, Chap. 1. S.L. Tan (Ed.).
13. Cho H., Mukherjee S., Palasuberniam P., Pillow L., Bilgin B., Nezich C., Walton S.P., Feig M., Chan C. Molecular mechanism by which palmitate inhibits PKR autophosphorylation. Biochemistry 2011, 50(6):1110-1119.
14. Clark V.C., Peter J.A., Nelson D.R. New therapeutic strategies in HCV: second-generation protease inhibitors. Liver Int. 2013, 33(1):80-84.
15. Cooksley W.G. The role of interferon therapy in hepatitis B. MedGenMed: Medscape General Medicine 2004, 6(1):16.
16. De Rueda P.M., Casado J., Paton R., Quintero D., Palacios A., Gila A., Quiles R., León J., Ruiz-Extremera A., Salmerón J. Mutations in E2-PePHD, NS5A-PKRBD, NS5A-ISDR and NS5A-V3 of hepatitis C virus genotype 1 and their relationships to pegylated interferon-ribavirin treatment responses. J. Virol. 2008, 82(13):6644-6653.
17. De Veer M.J., Holko M., Frevel M., Walker E., Der S., Paranjape J.M., Silverman R.H., Williams B.R. Functional classification of interferon-stimulated genes identified using microarrays. J. Leukocyte Biol. 2001, 69(6):912-920.
18. De Weerd N.A., Samarajiwa S.A., Hertzog P.J. Type I interferon receptors: biochemistry and biological functions. J. Biol. Chem. 2007, 282(28):20053-20057.
19. Deltenre P., Louvet A., Lemoine M., Mourad A., Fartoux L., Moreno C., Henrion J., Mathurin P., Serfaty L. Impact of insulin resistance on sustained response in HCV patients treated with pegylated interferon and ribavirin: a meta-analysis. J. Hepatol. 2011, 55(6):1187-1194.
20. Donnelly R.P., Kotenko S.V. Interferon-lambda: a new addition to an old family. J. Interferon Cytokine Res. 2010, 30(8):555-564.
21. Dunlevy F., McElvaney N.G., Greene C.M. TLR3 Sensing of viral infection. Open Infect. Dis. J. 2010, 4:1-10.
22. Enomoto N., Sakuma I., Asahina Y., Kurosaki M., Murakami T., Yamamoto C., Izumi N., Marumo F., Sato C. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. Sensitivity to interferon is conferred by amino acid substitutions in the NS5A region. J. Clin. Invest. 1995, 96:224-230.
23. Enomoto N., Sakuma I., Asahina Y., Kurosaki M., Murakami T., Yamamoto C., Ogura Y., Izumi N., Marumo F., Sato C. Mutations in the nonstructural protein 5a gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N. Engl. J. Med. 1996, 334:77-81.
24. Fensterl V., Sen G.C. Interferons and viral infections. BioFactors 2009, 35(1):14-20.
25. Fukuhara T., Taketomi A., Okano S., Ikegami T., Soejima Y., Shirabe K., Maehara Y. Mutations in hepatitis C virus genotype 1b and the sensitivity of interferon-ribavirin therapy after liver transplantation. J. Hepatol. 2009, 52(5):672-680.
26. Funaoka Y., Sakamoto N., Suda G., Itsui Y., Nakagawa M., Kakinuma S., Watanabe T., Mishima K., Ueyama M., Onozuka I., Nitta S., Kitazume A., Kiyohashi K., Murakawa M., Azuma S., Tsuchiya K., Watanabe M. Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91. J. Virol. 2011, 85(12):5986-5994.
27. Gale M.J., Foy E.M. Evasion of intracellular host defence by hepatitis C virus. Nature 2005, 436(7053):939-945.
28. Haller O., Kochs G., Weber F. Interferon, Mx, and viral countermeasures. Cytokine Growth Factor Rev. 2007, 18(5-6):425-433.
29. Hamdi N., El-Akel W., El-Serafy M., Esmat G., Sarrazin C., Abdelaziz A.I. Transcriptional response of MxA, PKR and SOCS3 to interferon-based therapy in HCV genotype 4-infected patients and contribution of p53 to host antiviral response. Intervirology 2012, 55(3):210-218.
30. Heim M. Interferons and hepatitis C virus. Swiss Med. Wkly. 2012, 142:w13586.
31. Hourioux C., Patient R., Morin A., Blanchard E., Moreau A., Trassard S., Giraudeau B., Roingeard P. The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model. Gut 2007, 56(9):1302-1308.
32. Huang Y., Feld J.J., Sapp R.K., Nanda S., Lin J.H., Blatt L.M., Fried M.W., Murthy K., Liang T.J. Defective hepatic response to interferon and activation of suppressor of cytokine signaling 3 in chronic hepatitis C. Gastroenterology 2007, 132:733-744.
33. Jamal I.S., Yusuf S., Azhar M., Jamall S. Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?. World J. Gastroenterol. 2008, 14(43):6627-6631.
34. Kato N. Genome of human hepatitis C virus (HCV): gene organization, sequence diversity, and variation. Microb. Comp. Genomics 2000, 5(3):129-151.
35. Kobayashi M., Watanabe K., Ishigami M., Murase K., Ito H., Ukai K., Yano M., Takagi K., Hattori M., Kakumu S., Yoshioka K. Amino acid substitutions in the nonstructural region 5A of hepatitis C virus geno- types 2a and 2b and its relation to viral load and response to interferon. Am. J. Gastroenterol. 2002, 97:988-998.
36. Kozuka R., Enomoto M., Hai H., Ogawa T., Nakaya M., Hagihara A., Fujii H., Kobayashi S., Iwai S., Morikawa H., Tamori A., Kawada N. Changes in sequences of core region, interferon sensitivity-determining region and interferon and ribavirin resistance-determining region of hepatitis C virus genotype 1 during interferon-alpha and ribavirin therapy, and efficacy of retreatment. Hepatol Res. 2012, 42(12):1157-1167.
37. Kumar D., Farrell G.C., Fung C., George J. Hepatitis C virus genotype 3 is cytopathic to hepatocytes: reversal of hepatic steatosis after sustained therapeutic response. Epatology 2002, 36(5):1266.
38. Kumthip K., Chusri P., Jilg N., Zhao L., Fusco D.N., Zhao H., Goto K., Cheng D., Schaefer E.A., Zhang L., Pantip C., Thongsawat S., O'Brien A., Peng L.F., Maneekarn N., Chung R.T., Lin W. Hepatitis C virus NS5A disrupts STAT1 phosphorylation and suppresses type I interferon signaling. J. Virol. 2012, 86(16):8581-8591.
39. Le Guillou-Guillemette H., Vallet S., Gaudy-Graffin C., Payan C., Pivert A., Goudeau A., Lunel-Fabiani F. Genetic diversity of the hepatitis C virus: impact and issues in the antiviral therapy. World J. Gastroenterol. 2007, 13(17):2416-2426.
40. Li K., Foy E., Ferreon J.C., Nakamura M., Ferreon A.C., Ikeda M., Ray S.C., Gale M., Lemon S.M. 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 2005, 102(8):2992-2997.
41. Lin R.J., Liao C.L., Lin E., Lin Y.L. Blocking of the alpha interferon-induced Jak-stat signaling pathway by Japanese encephalitis virus infection. J. Virol. 2004, 78(17):9285-9294.
42. Lindh M., Lagging M., Arnholm B., Eilard A., Nilsson S., Norkrans G., Söderholm J., Wahlberg T., Wejstål R., Westin J., Hellstrand K. IL28B polymorphisms determine early viral kinetics and treatment outcome in patients receiving peginterferon/ribavirin for chronic hepatitis C genotype 1. J Viral Hepat. 2011, 18(7):325-331.
43. Liu Y.J. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 2005, 23:275-306.
44. Manns M.P., Foster G.R., Rockstroh J.K., Zeuzem S., Zoulim F., Houghton M. The way forward in HCV treatment: finding the right path. Nat. Rev. Drug Discov. 2007, 6(12):991-1000.
45. Meier V., Ramadori G. Hepatitis C virus virology and new treatment targets. Expert Rev. Anti Infect. Ther. 2009, 7(3):329-350.
46. Moradpour D., Penin F., Rice C.M. Replication of hepatitis C virus. Nat. Rev. Microbiol. 2007, 5(6):453-463.
47. Morgan T.R., Ghany M.G., Kim H.Y., Snow K.K., Shiffman M.L., De Santo J.L., Lee W.M., Di Bisceglie A.M., Bonkovsky H.L., Dienstag J.L., Morishima C., Lindsay K.L., Lok A.S. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology 2010, 52(3):833-844. HALT-C Trial Group.
48. NIH Consensus Statement on Management of hepatitis C, 2002. NIH Consens State Sci Statements. 19 (3), pp. 1-46.
49. Pawlotsky J.M. Hepatitis C virus genetic variability: pathogenic and clinical implications. Clin. Liver Dis. 2003, 7:45-66.
50. Pawlotsky J.M. New antiviral agents for hepatitis C. F1000. Biol. Rep. 2012, 4:5.
51. Pawlotsky J.M., Pellerin M., Bouvier M., Roudot-Thoraval F., Germanidis G., Bastie A., Darthuy F., Rémiré J., Soussy C.J., Dhumeaux D. Genetic complexity of the hypervariable region 1 (HVR1) of hepatitis C virus (HCV): influence on the characteristics of the infection and responses to interferon alfa therapy in patients with chronic hepatitis C. J. Med. Virol. 1998, 54(4):256-264.
52. Pazienza V., Vinciguerra M., Andriulli A., Mangia A. Hepatitis C virus core protein genotype 3a increases SOCS-7 expression through PPAR-{gamma} in Huh-7 cells. J. Gen. Virol. 2010, 91(Pt 7):1678-1686.
53. Penin F., Dubuisson J., Rey F.A., Moradpour D., Pawlotsky J.M. Structural biology of hepatitis C virus. Hepatology 2004, 39:5-19.
54. Pileri P., Uematsu Y., Campagnoli S., Galli G., Falugi F., Petracca R., Weiner A.J., Houghton M., Rosa D., Grandi G., Abrignani S. Binding of hepatitis C virus to CD81. Science 1998, 282:938-941.
55. Platanias L.C. Mechanisms of type-I- and type-II-interferon-mediated signaling. Nat. Rev. Immunol. 2005, 5(5):375-386.
56. Qadri I., Iwahashi M., Simon F. Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3. Biochim Biophys Acta. 2002, 1592:193-204.
57. Qadri I., Iwahashi M., Cappasso J., Hopken M.W., Flores S., Schaack J., Simon F.R. Induced oxidative stress and activated expression of manganese superoxide dismutase (MnSOD) in HCV-replicating cells: role of JNK, p38MAPK & AP-1. Biochem. J. 2004, 10:416-417.
58. Qadri I., Hu L.J., Iwahashi M., Al-Zuahbi S., Quattrochi L., Simon F.R. Interaction of hepatocyte nuclear factors in transcriptional regulation of tissue specific hormonal expression of human multidrug resistance associated protein-2 (ABCC2). Pharmacol. Toxicol. 2009, 234(3):281-292.
59. Qadri I., Choudhury M., Rahman S.M., Knotts T.A., Janssen R.C., Schaack J., Iwahashi M., Puljak L., Simon F.R., Kilic G., Fitz J.G., Friedman J.E. Increased phosphoenolpyruvate carboxykinase gene expression and steatosis during hepatitis C virus subgenome replication: role of nonstructural component 5A and CCAAT/enhancer-binding protein β. J. Biol. Chem. 2012, 287(44):37340-37351.
60. Romero-Gómez M. Insulin resistance and hepatitis C. World J. Gastroenterol. 2006, 12(44):7075-7080.
61. Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y., Choo Q.L., Houghton M., Kuo G. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc. Natl. Acad. Sci. USA 1990, 87:6547-6549.
62. Sarasin-Filipowicz M., Oakeley E.J., Duong F.H., Christen V., Terracciano L., Filipowicz W., Heim M.H. Interferon signaling and treatment outcome in chronic hepatitis C. Proc. Natl. Acad. Sci. USA 2008, 105(19):7034-7039.
63. Sarrazin C., Hézode C., Zeuzem S., Pawlotsky J.M. Antiviral strategies in hepatitis C virus infection. J. Hepatol. 2012, 56(Suppl):S88-S100.
64. Shao R.X., Zhang L., Peng L.F., Sun E., Chung W.J., Jang J.Y., Tsai W.L., Hyppolite G., Chung R.T. Suppressor of cytokine signaling 3 suppresses hepatitis C virus replication in an mTOR-dependent manner. J. Virol. 2010, 84(12):6060-6069.
65. Sharieff K.A., Duncan D., Younossi Z. Advances in treatment of chronic hepatitis C: 'pegylated' interferons. Cleve. Clin. J. Med. 2002, 69(2):155-159.
66. Sheikh M.Y., Choi J., Qadri I., Friedman J.E., Sanyal A.J. Hepatitis C virus infection: molecular pathways to metabolic syndrome. Hepatology 2008, 47:2127-2133.
67. Simmonds P. Genetic diversity and evolution of hepatitis C virus - 15 years on. J. Gen. Virol. 2004, 85(Pt 11):3173-3188.
68. Simmonds P., Bukh J., Combet C., Deléage G., Enomoto N., Feinstone S., Halfon P., Inchauspé G., Kuiken C., Maertens G., Mizokami M., Murphy D., Okamoto H., Pawlotsky J., Penin F., Sablon E., Shin-I T., Stuyver L., Thiel H., Viazov S., Weiner A., Widell A. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005, 42(4):962-973.
69. Slev P. Host genomics and HCV personalized medicine. Ann. Clin. Lab. Sci. 2012, 42(4):363-369.
70. Syed G.H., Amako Y., Siddiqui A. Hepatitis C virus hijacks host lipid metabolism. Trends Endocrinol. Metab. 2010, 21(1):33-40.
71. Taylor D.R., Shi S.T., Romano P.R., Barber G.N., Lai M.M. Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 1999, 285(5424):107-110.
72. Vermehren J., Sarrazin C. New hepatitis C therapies in clinical development. Eur. J. Med. Res. 2011, 16:303-314.
73. Vermehren J., Sarrazin C. The role of resistance in HCV treatment. Best Pract. Res. Clin. Gastroenterol. 2012, 26(4):487-503.
74. Walsh M.J., Jonsson J.R., Richardson M.M., Lipka G.M., Purdie D.M., Clouston A.D., Powell E.E. Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1. Gut 2006, 55:529-535.
75. Yoneda S., Umemura T., Katsuyama Y., Kamijo A., Joshita S., Komatsu M., Ichijo T., Matsumoto A., Yoshizawa K., Ota M., Tanaka E. Association of serum cytokine levels with treatment response to pegylated interferon and ribavirin therapy in genotype 1 chronic hepatitis C patients. J. Infect. Dis. 2011, 203(8):1087-1095. Nagano Interferon Treatment Research Group.
76. Zhang L., Jilg N., Shao R.X., Lin W., Fusco D.N., Zhao H., Goto K., Peng L.F., Chen W.C., Chung R.T. IL28B inhibits hepatitis C virus replication through the JAK-STAT pathway. J. Hepatol. 2011, 55(2):289-298.