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01-01-2014 | Brief Review

Role of different regions of the hepatitis C virus genome in the therapeutic response to interferon-based treatment

Authors: Saba Khaliq, Noreen Latief, Shah Jahan

Published in: Archives of Virology | Issue 1/2014

Abstract

Hepatitis C virus (HCV) is considered a significant risk factor in HCV-induced liver diseases and development of hepatocellular carcinoma (HCC). Nucleotide substitutions in the viral genome result in its diversification into quasispecies, subtypes and distinct genotypes. Different genotypes vary in their infectivity and immune response due to these nucleotide/amino acid variations. The current combination treatment for HCV infection is pegylated interferon α (PEG-IFN-α) with ribavirin, with a highly variable response rate mainly depending upon the HCV genotype. Genotypes 2 and 3 are found to respond better than genotypes 1 and 4, which are more resistant to IFN-based therapies. Different studies have been conducted worldwide to explore the basis of this difference in therapy response, which identified some putative regions in the HCV genome, especially in Core and NS5a, and to some extent in the E2 region, containing specific sequences in different genotypes that act differently with respect to the IFN response. In the review, we try to summarize the role of HCV proteins and their nucleotide sequences in association with treatment outcome in IFN-based therapy.

Giannini C, Brechot C (2003) Hepatitis C virus biology. Cell Death Differ 10(Suppl 1):S27–S38PubMed

Hoofnagle JH (2002) Course and outcome of hepatitis C. Hepatology 36:S21–S29PubMed

Lavanchy D (2011) Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 17:107–115PubMed

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362PubMed

Tsukiyama-Kohara K, Iizuka N, Kohara M, Nomoto A (1992) Internal ribosome entry site within hepatitis C virus RNA. J Virol 66:1476–1483PubMedCentralPubMed

Okamoto H, Okada S, Sugiyama Y, Yotsumoto S, Tanaka T, Yoshizawa H, Tsuda F, Miyakawa Y, Mayumi M (1990) The 5’-terminal sequence of the hepatitis C virus genome. Jpn J Exp Med 60:167–177PubMed

Tanaka T, Kato N, Cho MJ, Sugiyama K, Shimotohno K (1996) Structure of the 3’ terminus of the hepatitis C virus genome. J Virol 70:3307–3312PubMedCentralPubMed

Weiner AJ, Brauer MJ, Rosenblatt J, Richman KH, Tung J, Crawford K, Bonino F, Saracco G, Choo QL, Houghton M (1991) Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology 180:842–848PubMed

Lohmann V, Roos A, Korner F, Koch JO, Bartenschlager R (2000) Biochemical and structural analysis of the NS5B RNA-dependent RNA polymerase of the hepatitis C virus. J Viral Hepat 7:167–174PubMed

10.

Kuiken C, Simmonds P (2009) Nomenclature and numbering of the hepatitis C virus. Methods Mol Biol 510:33–53PubMed

11.

McHutchison JG, Fried MW (2003) Current therapy for hepatitis C: pegylated interferon and ribavirin. Clin Liver Dis 7:149–161PubMed

12.

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J (2002) Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975–982PubMed

13.

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358:958–965PubMed

14.

Kamal SM (2011) Hepatitis C virus genotype 4 therapy: progress and challenges. Liver Int 31(Suppl 1):45–52PubMed

15.

Ferenci P, Fried MW, Shiffman ML, Smith CI, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Chaneac M, Reddy KR (2005) Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol 43:425–433PubMed

16.

Berg T, von WM, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, Zeuzem S (2006) Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 130:1086–1097PubMed

17.

McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS (2009) Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 361:580–593PubMed

18.

Gale M Jr, Foy EM (2005) Evasion of intracellular host defence by hepatitis C virus. Nature 436:939–945PubMed

19.

Burke KP, Cox AL (2010) Hepatitis C virus evasion of adaptive immune responses: a model for viral persistence. Immunol Res 47:216–227PubMedCentralPubMed

20.

Hofmann WP, Zeuzem S, Sarrazin C (2005) Hepatitis C virus-related resistance mechanisms to interferon alpha-based antiviral therapy. J Clin Virol 32:86–91PubMed

21.

Tachi Y, Katano Y, Honda T, Hayashi K, Ishigami M, Itoh A, Hirooka Y, Nakano I, Samejima Y, Goto H (2010) Impact of amino acid substitutions in the hepatitis C virus genotype 1b core region on liver steatosis and hepatic oxidative stress in patients with chronic hepatitis C. Liver Int 30(4):554–559

22.

Khaliq S, Jahan S, Pervaiz A (2011) Sequence variability of HCV Core region: important predictors of HCV induced pathogenesis and viral production. Infect Genet Evol 11:543–556PubMed

23.

Akuta N, Suzuki F, Sezaki H, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Watahiki S, Sato J, Matsuda M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2005) Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferon-ribavirin combination therapy. Intervirology 48:372–380PubMed

24.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2009) Amino acid substitutions in the hepatitis C virus core region of genotype 1b are the important predictor of severe insulin resistance in patients without cirrhosis and diabetes mellitus. J Med Virol 81:1032–1039PubMed

25.

Clemens MJ (1997) PKR—a protein kinase regulated by double-stranded RNA. Int J Biochem Cell Biol 29:945–949PubMed

26.

Grandvaux N, tenOever BR, Servant MJ, Hiscott J (2002) The interferon antiviral response: from viral invasion to evasion. Curr Opin Infect Dis 15:259–267PubMed

27.

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 230:217–227PubMed

28.

Sarrazin C, Berg T, Lee JH, Ruster B, Kronenberger B, Roth WK, Zeuzem S (2000) Mutations in the protein kinase-binding domain of the NS5A protein in patients infected with hepatitis C virus type 1a are associated with treatment response. J Infect Dis 181:432–441PubMed

29.

Chevaliez S, Pawlotsky JM (2007) Interferon-based therapy of hepatitis C. Adv Drug Deliv Rev 59:1222–1241PubMed

30.

Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J (2003) Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 38:645–652PubMed

31.

Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264PubMed

32.

Foster GR, Finter NB (1998) Are all type I human interferons equivalent? J Viral Hepat 5:143–152PubMed

33.

Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR (1995) Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem 270:21606–21611PubMed

34.

Novick D, Cohen B, Rubinstein M (1994) The human interferon alpha/beta receptor: characterization and molecular cloning. Cell 77:391–400PubMed

35.

Yatsuhashi H, Fujino T, Matsumoto T, Inoue O, Koga M, Yano M (1999) Immunohistochemical analysis of hepatic interferon alpha-beta receptor level: relationship between receptor expression and response to interferon therapy in patients with chronic hepatitis C. J Hepatol 30:995–1003PubMed

36.

Mizukoshi E, Kaneko S, Yanagi M, Ohno H, Kaji K, Terasaki S, Shimoda A, Matsushita E, Kobayashi K (1998) Expression of interferon alpha/beta receptor in the liver of chronic hepatitis C patients. J Med Virol 56:217–223PubMed

37.

Mathai J, Shimoda K, Banner BF, Mori M, Bonkovsky HL, Barnard GF (1999) IFN-alpha receptor mRNA expression in a United States sample with predominantly genotype 1a/I chronic hepatitis C liver biopsies correlates with response to IFN therapy. J Interferon Cytokine Res 19:1011–1018PubMed

38.

Yamaguchi Y, Hino K, Fujiwara D, Ren F, Katoh Y, Satoh Y, Okita K (2002) Expression of type I interferon receptor in liver and peripheral blood mononuclear cells in chronic hepatitis C patients. Dig Dis Sci 47:1611–1617PubMed

39.

Larner A, Reich NC (1996) Interferon signal transduction. Biotherapy 8:175–181PubMed

40.

Parmar S, Platanias LC (2003) Interferons: mechanisms of action and clinical applications. Curr Opin Oncol 15:431–439PubMed

41.

Chen X, Bhandari R, Vinkemeier U, Van Den AF, Darnell JE Jr, Kuriyan J (2003) A reinterpretation of the dimerization interface of the N-terminal domains of STATs. Protein Sci 12:361–365PubMed

42.

Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285:1–24PubMed

43.

ten HJ, de J, Fu Y, Zhu W, Tremblay M, David M, Shuai K (2002) Identification of a nuclear Stat1 protein tyrosine phosphatase. Mol Cell Biol 22:5662–5668

44.

Liu KD, Gaffen SL, Goldsmith MA (1998) JAK/STAT signaling by cytokine receptors. Curr Opin Immunol 10:271–278PubMed

45.

Der SD, Zhou A, Williams BR, Silverman RH (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA 95:15623–15628PubMed

46.

Durbin RK, Mertz SE, Koromilas AE, Durbin JE (2002) PKR protection against intranasal vesicular stomatitis virus infection is mouse strain dependent. Viral Immunol 15:41–51PubMed

47.

Kochs G, Haller O (1999) Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids. Proc Natl Acad Sci USA 96:2082–2086PubMed

48.

Zhu H, Zhao H, Collins CD, Eckenrode SE, Run Q, McIndoe RA, Crawford JM, Nelson DR, She JX, Liu C (2003) Gene expression associated with interferon alfa antiviral activity in an HCV replicon cell line. Hepatology 37:1180–1188PubMed

49.

Taylor DR, Shi ST, Romano PR, Barber GN, Lai MM (1999) Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein. Science 285:107–110PubMed

50.

Hui CK, Yuen MF, Sablon E, Chan AO, Wong BC, Lai CL (2003) Interferon and ribavirin therapy for chronic hepatitis C virus genotype 6: a comparison with genotype 1. J Infect Dis 187:1071–1074PubMed

51.

Yuen MF, Lai CL (2006) Response to combined interferon and ribavirin is better in patients infected with hepatitis C virus genotype 6 than genotype 1 in Hong Kong. Intervirology 49:96–98PubMed

52.

Derbala M, Amer A, Bener A, Lopez AC, Omar M, El GM (2005) Pegylated interferon-alpha 2b-ribavirin combination in Egyptian patients with genotype 4 chronic hepatitis. J Viral Hepat 12:380–385PubMed

53.

Legrand-Abravanel F, Nicot F, Boulestin A, Sandres-Saune K, Vinel JP, Alric L, Izopet J (2005) Pegylated interferon and ribavirin therapy for chronic hepatitis C virus genotype 4 infection. J Med Virol 77:66–69PubMed

54.

Buti M, Valdes A, Sanchez-Avila F, Esteban R, Lurie Y (2003) Extending combination therapy with peginterferon alfa-2b plus ribavirin for genotype 1 chronic hepatitis C late responders: a report of 9 cases. Hepatology 37:1226–1227PubMed

55.

Sanchez-Tapias JM, Diago M, Escartin P, Enriquez J, Romero-Gomez M, Barcena R, Crespo J, Andrade R, Martinez-Bauer E, Perez R, Testillano M, Planas R, Sola R, Garcia-Bengoechea M, Garcia-Samaniego J, Munoz-Sanchez M, Moreno-Otero R (2006) Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology 131:451–460PubMed

56.

Pearlman BL, Ehleben C, Saifee S (2007) Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology 46:1688–1694PubMed

57.

Blindenbacher A, Duong FH, Hunziker L, Stutvoet ST, Wang X, Terracciano L, Moradpour D, Blum HE, Alonzi T, Tripodi M, La MN, Heim MH (2003) Expression of hepatitis c virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology 124:1465–1475PubMed

58.

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 17:488–490PubMed

59.

Thomis DC, Samuel CE (1995) Mechanism of interferon action: characterization of the intermolecular autophosphorylation of PKR, the interferon-inducible, RNA-dependent protein kinase. J Virol 69:5195–5198PubMedCentralPubMed

60.

Yahoo N, Sabahi F, Shahzamani K, Malboobi MA, Jabbari H, Sharifi H, Mousavi-Fard SH, Merat S (2011) Mutations in the E2 and NS5A regions in patients infected with hepatitis C virus genotype 1a and their correlation with response to treatment. J Med Virol 83:1332–1337PubMed

61.

Santolini E, Migliaccio G, La MN (1994) Biosynthesis and biochemical properties of the hepatitis C virus core protein. J Virol 68:3631–3641PubMedCentralPubMed

62.

it Goughoulte M, Hourioux C, Patient R, Trassard S, Brand D, Roingeard P (2006) Core protein cleavage by signal peptide peptidase is required for hepatitis C virus-like particle assembly. J Gen Virol 87:855–860

63.

Targett-Adams P, Hope G, Boulant S, McLauchlan J (2008) Maturation of hepatitis C virus core protein by signal peptide peptidase is required for virus production. J Biol Chem 283:16850–16859PubMed

64.

Ciccaglione AR, Stellacci E, Marcantonio C, Muto V, Equestre M, Marsili G, Rapicetta M, Battistini A (2007) Repression of interferon regulatory factor 1 by hepatitis C virus core protein results in inhibition of antiviral and immunomodulatory genes. J Virol 81:202–214PubMedCentralPubMed

65.

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 80:9226–9235PubMedCentralPubMed

66.

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 73:536–547PubMed

67.

Ishii K, Shinohara M, Sawa M, Kogame M, Higami K, Sano M, Morita T, Sumino Y (2010) Interferon alpha receptor 2 expression by peripheral blood monocytes in patients with a high viral load of hepatitis C virus genotype 1 showing substitution of amino Acid 70 in the core region. Intervirology 53:105–110PubMed

68.

Akuta N, Suzuki F, Sezaki H, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Watahiki S, Sato J, Kobayashi M, Arase Y, Ikeda K, Kumada H (2006) Predictive factors of virological non-response to interferon-ribavirin combination therapy for patients infected with hepatitis C virus of genotype 1b and high viral load. J Med Virol 78:83–90PubMed

69.

Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2007) Amino acid substitutions in the hepatitis C virus core region are the important predictor of hepatocarcinogenesis. Hepatology 46:1357–1364PubMed

70.

Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Miyakawa Y, Kumada H (2007) Prediction of response to pegylated interferon and ribavirin in hepatitis C by polymorphisms in the viral core protein and very early dynamics of viremia. Intervirology 50:361–368PubMed

71.

Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2007) Predictive factors of early and sustained responses to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b: amino acid substitutions in the core region and low-density lipoprotein cholesterol levels. J Hepatol 46:403–410PubMed

72.

Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2007) Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. J Med Virol 79:1686–1695PubMed

73.

Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Arase Y, Ikeda K, Kumada H (2008) Efficacy of low-dose intermittent interferon-alpha monotherapy in patients infected with hepatitis C virus genotype 1b who were predicted or failed to respond to pegylated interferon plus ribavirin combination therapy. J Med Virol 80:1363–1369PubMed

74.

Donlin MJ, Cannon NA, Yao E, Li J, Wahed A, Taylor MW, Belle SH, Di Bisceglie AM, Aurora R, Tavis JE (2007) Pretreatment sequence diversity differences in the full-length hepatitis C virus open reading frame correlate with early response to therapy. J Virol 81:8211–8224PubMedCentralPubMed

75.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2009) A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response. J Med Virol 81:452–458PubMed

76.

Takahashi K, Iwata K, Matsumoto M, Matsumoto H, Nakao K, Hatahara T, Ohta Y, Kanai K, Maruo H, Baba K, Hijikata M, Mishiro S (2001) Hepatitis C virus (HCV) genotype 1b sequences from fifteen patients with hepatocellular carcinoma: the ‘progression score’ revisited. Hepatol Res 20:161–171PubMed

77.

Fishman SL, Factor SH, Balestrieri C, Fan X, Dibisceglie AM, Desai SM, Benson G, Branch AD (2009) Mutations in the hepatitis C virus core gene are associated with advanced liver disease and hepatocellular carcinoma. Clin Cancer Res 15:3205–3213PubMedCentralPubMed

78.

Hayashi K, Katano Y, Ishigami M, Itoh A, Hirooka Y, Nakano I, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H (2011) Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated-interferon-alpha 2b and ribavirin combination therapy. J Viral Hepat 18:280–286PubMed

79.

Kurbanov F, Tanaka Y, Matsuura K, Sugauchi F, Elkady A, Khan A, Hasegawa I, Ohno T, Tokuda H, Mizokami M (2010) Positive selection of core 70Q variant genotype 1b hepatitis C virus strains induced by pegylated interferon and ribavirin. J Infect Dis 201:1663–1671PubMed

80.

Inoue Y, Hiramatsu N, Oze T, Yakushijin T, Mochizuki K, Fukuda K, Mita E, Haruna Y, Inoue A, Imai Y, Hosui A, Miyagi T, Yoshida Y, Tatsumi T, Kiso S, Kanto T, Kasahara A, Takehara T, Hayashi N (2011) Amino acid substitution in the core protein has no impact on relapse in hepatitis C genotype 1 patients treated with peginterferon and ribavirin. J Med Virol 83:419–427PubMed

81.

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 (2011) Analysis of interferon signaling by infectious hepatitis C virus clones with substitutions of core amino acids 70 and 91. J Virol 85:5986–5994PubMedCentralPubMed

82.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2009) Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 2a high viral load and virological response to interferon-ribavirin combination therapy. Intervirology 52:301–309PubMed

83.

El-Shamy A, Shoji I, Kim SR, Ide Y, Imoto S, Deng L, Yoon S, Fujisawa T, Tani S, Yano Y, Seo Y, Azuma T, Hotta H (2012) Sequence heterogeneity in NS5A of hepatitis C virus genotypes 2a and 2b and clinical outcome of pegylated-interferon/ribavirin therapy. PLoS One 7:e30513PubMedCentralPubMed

84.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2010) Amino acid substitutions in the hepatitis C virus core region of genotype 1b affect very early viral dynamics during treatment with telaprevir, peginterferon, and ribavirin. J Med Virol 82:575–582PubMed

85.

McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, Zeuzem S, Reesink HW, Garg J, Bsharat M, George S, Kauffman RS, Adda N, Di Bisceglie AM (2010) Telaprevir for previously treated chronic HCV infection. N Engl J Med 362:1292–1303PubMed

86.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H (2011) Amino acid substitutions in hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by antiviral therapy. J Med Virol 83:1016–1022PubMed

87.

El-Shamy A, Shoji I, El-Akel W, Bilasy SE, Deng L, El-Raziky M, Jiang DP, Esmat G, Hotta H (2012) NS5A sequence heterogeneity of hepatitis C virus genotype 4a predicts clinical outcome of pegylated-interferon-ribavirin therapy in Egyptian patients. J Clin Microbiol 50:3886–3892PubMedCentralPubMed

88.

Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S (1998) Binding of hepatitis C virus to CD81. Science 282:938–941PubMed

89.

Cochrane A, Orr A, Shaw ML, Mills PR, McCruden EA (2000) The amino acid sequence of the PKR-eIF2alpha phosphorylation homology domain of hepatitis C virus envelope 2 protein and response to interferon-alpha. J Infect Dis 182:1515–1518PubMed

90.

Brand SR, Kobayashi R, Mathews MB (1997) The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. J Biol Chem 272:8388–8395PubMed

91.

Blom N, Gammeltoft S, Brunak S (1999) Sequence and structure-based prediction of eukaryotic protein phosphorylation sites. J Mol Biol 294:1351–1362PubMed

92.

Bonnet MC, Weil R, Dam E, Hovanessian AG, Meurs EF (2000) PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex. Mol Cell Biol 20:4532–4542PubMedCentralPubMed

93.

Shirai M, Arichi T, Chen M, Masaki T, Nishioka M, Ikeda K, Takahashi H, Enomoto N, Saito T, Major ME, Nakazawa T, Akatsuka T, Feinstone SM, Berzofsky JA (1999) T cell recognition of hypervariable region-1 from hepatitis C virus envelope protein with multiple class II MHC molecules in mice and humans: preferential help for induction of antibodies to the hypervariable region. J Immunol 162:568–576PubMed

94.

Rafique S, Idrees M, Ilyas M, Hussain A, Ali M, Ali L, Butt S, Afzal S, Ur R, Saleem S (2011) Positional effect of phosphorylation sites 266 and 267 in the cytoplasmic domain of the E2 protein of hepatitis C virus 3a genotype: interferon resistance analysis via sequence alignment. Virol J 8:204PubMedCentralPubMed

95.

Sarrazin C, Bruckner M, Herrmann E, Ruster B, Bruch K, Roth WK, Zeuzem S (2001) Quasispecies heterogeneity of the carboxy-terminal part of the E2 gene including the PePHD and sensitivity of hepatitis C virus 1b isolates to antiviral therapy. Virology 289:150–163PubMed

96.

Chayama K, Suzuki F, Tsubota A, Kobayashi M, Arase Y, Saitoh S, Suzuki Y, Murashima N, Ikeda K, Takahashi N, Kinoshita M, Kumada H (2000) Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy. Hepatology 32:1138–1144PubMed

97.

Berg T, Mas MA, Hohne M, Wiedenmann B, Hopf U, Schreier E (2000) Mutations in the E2-PePHD and NS5A region of hepatitis C virus type 1 and the dynamics of hepatitis C viremia decline during interferon alfa treatment. Hepatology 32:1386–1395PubMed

98.

Hung CH, Lee CM, Lu SN, Lee JF, Wang JH, Tung HD, Chen TM, Hu TH, Chen WJ, Changchien CS (2003) Mutations in the NS5A and E2-PePHD region of hepatitis C virus type 1b and correlation with the response to combination therapy with interferon and ribavirin. J Viral Hepat 10:87–94PubMed

99.

Saito T, Ito T, Ishiko H, Yonaha M, Morikawa K, Miyokawa A, Mitamura K (2003) Sequence analysis of PePHD within HCV E2 region and correlation with resistance of interferon therapy in Japanese patients infected with HCV genotypes 2a and 2b. Am J Gastroenterol 98:1377–1383PubMed

100.

Ukai K, Ishigami M, Yoshioka K, Kawabe N, Katano Y, Hayashi K, Honda T, Yano M, Goto H (2006) Mutations in carboxy-terminal part of E2 including PKR/eIF2alpha phosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b: their correlation with response to interferon monotherapy and viral load. World J Gastroenterol 12:3722–3728PubMed

101.

Gerotto M, Dal PF, Pontisso P, Noventa F, Gatta A, Alberti A (2000) Two PKR inhibitor HCV proteins correlate with early but not sustained response to interferon. Gastroenterology 119:1649–1655PubMed

102.

Bolcic F, Laufer N, Torres C, Cassino L, Reynoso R, Quarleri J (2012) Longitudinal analysis of the 5’UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients. Antiviral Res 95:72–81PubMed

103.

Afzal S, Idrees M, Akram M, Awan Z, Khubaib B, Aftab M, Fatima Z, Badar S, Hussain A (2010) Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation with response to interferon and ribavirin combination therapy in Pakistani patients. Virol J 7:377PubMedCentralPubMed

104.

Bagaglio S, Bruno R, Lodrini S, De Mitri MS, Andreone P, Loggi E, Galli L, Lazzarin A, Morsica G (2003) Genetic heterogeneity of hepatitis C virus (HCV) in clinical strains of HIV positive and HIV negative patients chronically infected with HCV genotype 3a. J Biol Regul Homeost Agents 17:153–161PubMed

105.

Lee SH, Kim YK, Kim CS, Seol SK, Kim J, Cho S, Song YL, Bartenschlager R, Jang SK (2005) E2 of hepatitis C virus inhibits apoptosis. J Immunol 175:8226–8235PubMed

106.

Owsianka AM, Timms JM, Tarr AW, Brown RJ, Hickling TP, Szwejk A, Bienkowska-Szewczyk K, Thomson BJ, Patel AH, Ball JK (2006) Identification of conserved residues in the E2 envelope glycoprotein of the hepatitis C virus that are critical for CD81 binding. J Virol 80:8695–8704PubMedCentralPubMed

107.

Smith DB (1999) Evolution of the hypervariable region of hepatitis C virus. J Viral Hepat 6(Suppl 1):41–46PubMed

108.

Hino K, Korenaga M, Orito E, Katoh Y, Yamaguchi Y, Ren F, Kitase A, Satoh Y, Fujiwara D, Okita K (2002) Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients. J Viral Hepat 9:194–201PubMed

109.

Alfonso V, Flichman DM, Sookoian S, Mbayed VA, Campos RH (2004) Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection. J Gen Virol 85:39–46PubMed

110.

Al-Qahtani AA, Rubino S, Al-Ahdal MN (2011) Sequence variation of the HVR1 region of Hepatitis C virus in response to interferon-alpha and ribavirin treatment. J Infect Dev Ctries 5:370–376PubMed

111.

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 285:110–113PubMed

112.

Kohashi T, Maekawa S, Sakamoto N, Kurosaki M, Watanabe H, Tanabe Y, Chen CH, Kanazawa N, Nakagawa M, Kakinuma S, Yamashiro T, Itsui Y, Koyama T, Enomoto N, Watanabe M (2006) Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication. J Viral Hepat 13:582–590PubMed

113.

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 300:1145–1148PubMed

114.

Yao ZQ, Eisen-Vandervelde A, Waggoner SN, Cale EM, Hahn YS (2004) Direct binding of hepatitis C virus core to gC1qR on CD4⁺ and CD8⁺ T cells leads to impaired activation of Lck and Akt. J Virol 78:6409–6419PubMedCentralPubMed

115.

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 18:5208–5218PubMedCentralPubMed

116.

Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, Ogura Y, Izumi N, Marumo F, Sato C (1996) Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 334:77–81PubMed

117.

Nakano I, Fukuda Y, Katano Y, Nakano S, Kumada T, Hayakawa T (1999) Why is the interferon sensitivity-determining region (ISDR) system useful in Japan? J Hepatol 30:1014–1022PubMed

118.

Yen YH, Hung CH, Hu TH, Chen CH, Wu CM, Wang JH, Lu SN, Lee CM (2008) Mutations in the interferon sensitivity-determining region (nonstructural 5A amino acid 2209-2248) in patients with hepatitis C-1b infection and correlating response to combined therapy of pegylated interferon and ribavirin. Aliment Pharmacol Ther 27:72–79PubMed

119.

Murayama M, Katano Y, Nakano I, Ishigami M, Hayashi K, Honda T, Hirooka Y, Itoh A, Goto H (2007) A mutation in the interferon sensitivity-determining region is associated with responsiveness to interferon-ribavirin combination therapy in chronic hepatitis patients infected with a Japan-specific subtype of hepatitis C virus genotype 1B. J Med Virol 79:35–40PubMed

120.

Watanabe K, Yoshioka K, Yano M, Ishigami M, Ukai K, Ito H, Miyata F, Mizutani T, Goto H (2005) Mutations in the nonstructural region 5B of hepatitis C virus genotype 1b: their relation to viral load, response to interferon, and the nonstructural region 5A. J Med Virol 75:504–512PubMed

121.

Zeuzem S, Lee JH, Roth WK (1997) Mutations in the nonstructural 5A gene of European hepatitis C virus isolates and response to interferon alfa. Hepatology 25:740–744PubMed

122.

Murphy MD, Rosen HR, Marousek GI, Chou S (2002) Analysis of sequence configurations of the ISDR, PKR-binding domain, and V3 region as predictors of response to induction interferon-alpha and ribavirin therapy in chronic hepatitis C infection. Dig Dis Sci 47:1195–1205PubMed

123.

de Munoz RP, Casado J, Paton R, Quintero D, Palacios A, Gila A, Quiles R, Leon J, Ruiz-Extremera A, Salmeron J (2008) 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 82:6644–6653

124.

Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, Yamamoto C, Izumi N, Marumo F, Sato C (1995) 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 96:224–230PubMedCentralPubMed

125.

Watanabe H, Enomoto N, Nagayama K, Izumi N, Marumo F, Sato C, Watanabe M (2001) Number and position of mutations in the interferon (IFN) sensitivity-determining region of the gene for nonstructural protein 5A correlate with IFN efficacy in hepatitis C virus genotype 1b infection. J Infect Dis 183:1195–1203PubMed

126.

Kmieciak D, Kruszyna L, Migdalski P, Lacinski M, Juszczyk J, Trzeciak WH (2006) Mutations within protein kinase R-binding domain of NS5A protein of hepatitis C virus (HCV) and specificity of HCV antibodies in pretreatment sera of HCV-chronically infected patients and their effect on the result of treatment. Jpn J Infect Dis 59:92–99PubMed

127.

Brillet R, Penin F, Hezode C, Chouteau P, Dhumeaux D, Pawlotsky JM (2007) The nonstructural 5A protein of hepatitis C virus genotype 1b does not contain an interferon sensitivity-determining region. J Infect Dis 195:432–441PubMed

128.

Nousbaum J, Polyak SJ, Ray SC, Sullivan DG, Larson AM, Carithers RL Jr, Gretch DR (2000) Prospective characterization of full-length hepatitis C virus NS5A quasispecies during induction and combination antiviral therapy. J Virol 74:9028–9038PubMedCentralPubMed

129.

Schiappa DA, Mittal C, Brown JA, Mika BP (2002) Relationship of hepatitis C genotype 1 NS5A sequence mutations to early phase viral kinetics and interferon effectiveness. J Infect Dis 185:868–877PubMed

130.

Enomoto N, Maekawa S (2010) HCV genetic elements determining the early response to peginterferon and ribavirin therapy. Intervirology 53:66–69PubMed

131.

Murakami T, Enomoto N, Kurosaki M, Izumi N, Marumo F, Sato C (1999) Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection. Hepatology 30:1045–1053PubMed

132.

Hayashi K, Katano Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Nakano I, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H (2009) Mutations in the interferon sensitivity-determining region of hepatitis C virus genotype 2a correlate with response to pegylated-interferon-alpha 2a monotherapy. J Med Virol 81:459–466PubMed

133.

Reddy KR, Hoofnagle JH, Tong MJ, Lee WM, Pockros P, Heathcote EJ, Albert D, Joh T (1999) Racial differences in responses to therapy with interferon in chronic hepatitis C.Consensus Interferon Study Group. Hepatology 30:787–793PubMed

134.

Missiha S, Heathcote J, Arenovich T, Khan K (2007) Impact of Asian race on response to combination therapy with peginterferon alfa-2a and ribavirin in chronic hepatitis C. Am J Gastroenterol 102:2181–2188PubMed

135.

Fukuhara T, Takeishi K, Toshima T, Morita K, Ueda S, Iguchi T, Nagata S, Sugimachi K, Ikegami T, Gion T, Soejima Y, Taketomi A, Maehara Y (2010) Impact of amino acid substitutions in the core region of HCV on multistep hepatocarcinogenesis. Hepatol Res 40:171–178PubMed

136.

Zhou DX, Chan PK, Zhang T, Tully DC, Tam JS (2010) Sequence diversity of hepatitis C virus 6a within the extended interferon sensitivity-determining region correlates with interferon-alpha/ribavirin treatment outcomes. Virus Res 153:44–49PubMed

137.

Frangeul L, Cresta P, Perrin M, Duverlie G, Khorsi H, Musset L, Opolon P, Huraux JM, Lunel F (1998) Pattern of HCV antibodies with special reference to NS5A reactivity in HCV-infected patients: relation to viral genotype, cryoglobulinemia and response to interferon. J Hepatol 28:538–543PubMed

138.

Ploegh HL (1998) Viral strategies of immune evasion. Science 280:248–253PubMed

139.

Uzicanin S, Hu YW, Alsousi H, Pelchat M, Rocheleau L, Nair RC, Brown EG (2012) Hepatitis C virus: The role of molecular mimicry in response to interferon treatment. J Med Virol 84:1571–1585PubMed

140.

Chisari FV (2005) Unscrambling hepatitis C virus-host interactions. Nature 436:930–932PubMed

141.

Sarrazin C, Herrmann E, Bruch K, Zeuzem S (2002) Hepatitis C virus nonstructural 5A protein and interferon resistance: a new model for testing the reliability of mutational analyses. J Virol 76:11079–11090PubMedCentralPubMed

142.

Macquillan GC, Niu X, Speers D, English S, Garas G, Harnett GB, Reed WD, Allan JE, Jeffrey GP (2004) Does sequencing the PKRBD of hepatitis C virus NS5A predict therapeutic response to combination therapy in an Australian population? J Gastroenterol Hepatol 19:551–557PubMed

143.

Layden-Almer JE, Kuiken C, Ribeiro RM, Kunstman KJ, Perelson AS, Layden TJ, Wolinsky SM (2005) Hepatitis C virus genotype 1a NS5A pretreatment sequence variation and viral kinetics in African American and white patients. J Infect Dis 192:1078–1087PubMed

144.

Goyal A, Hofmann WP, Hermann E, Traver S, Hissar SS, Arora N, Blum HE, Zeuzem S, Sarrazin C, Sarin SK (2007) The hepatitis C virus NS5A protein and response to interferon alpha: mutational analyses in patients with chronic HCV genotype 3a infection from India. Med Microbiol Immunol 196:11–21PubMed

145.

Kadokura M, Maekawa S, Sueki R, Miura M, Komase K, Shindo H, Amemiya F, Uetake T, Inoue T, Sakamoto M, Nakagawa M, Sakamoto N, Watanabe M, Enomoto N (2011) Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy. Hepatol Int 5:789–799PubMed

146.

Kumthip K, Pantip C, Chusri P, Thongsawat S, O’Brien A, Nelson KE, Maneekarn N (2011) Correlation between mutations in the core and NS5A genes of hepatitis C virus genotypes 1a, 1b, 3a, 3b, 6f and the response to pegylated interferon and ribavirin combination therapy. J Viral Hepat 18:e117–e125PubMed

147.

Duverlie G, Khorsi H, Castelain S, Jaillon O, Izopet J, Lunel F, Eb F, Penin F, Wychowski C (1998) Sequence analysis of the NS5A protein of European hepatitis C virus 1b isolates and relation to interferon sensitivity. J Gen Virol 79(Pt 6):1373–1381PubMed

148.

Jardim AC, Yamasaki LH, de Queiroz AT, Bittar C, Pinho JR, Carareto CM, Rahal P, Mello IM (2009) Quasispecies of hepatitis C virus genotype 1 and treatment outcome with peginterferon and ribavirin. Infect Genet Evol 9:689–698PubMed

149.

Puig-Basagoiti F, Forns X, Furcic I, Ampurdanes S, Gimenez-Barcons M, Franco S, Sanchez-Tapias JM, Saiz JC (2005) Dynamics of hepatitis C virus NS5A quasispecies during interferon and ribavirin therapy in responder and non-responder patients with genotype 1b chronic hepatitis C. J Gen Virol 86:1067–1075PubMed

150.

Veillon P, Payan C, Le Guillou-Guillemette H, Gaudy C, Lunel F (2007) Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy. World J Gastroenterol 13:1195–1203PubMed

151.

Laufer N, Bolcic F, Rolon MJ, Martinez A, Reynoso R, Perez H, Salomon H, Cahn P, Quarleri J (2011) HCV RNA decline in the first 24 h exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin. Antiviral Res 90:92–97PubMedCentralPubMed

152.

El-Shamy A, Nagano-Fujii M, Sasase N, Imoto S, Kim SR, Hotta H (2008) Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology 48:38–47PubMed

153.

Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM (2004) Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140:346–355PubMed

154.

Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401PubMed

155.

Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109PubMed

156.

Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:1100–1104PubMed

157.

Rauch A, Kutalik Z, Descombes P, Cai T, di IJ, Mueller T, Bochud M, Battegay M, Bernasconi E, Borovicka J, Colombo S, Cerny A, Dufour JF, Furrer H, Gunthard HF, Heim M, Hirschel B, Malinverni R, Moradpour D, Mullhaupt B, Witteck A, Beckmann JS, Berg T, Bergmann S, Negro F, Telenti A, Bochud PY (2010) Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 138(1338–45):1345

158.

Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, Kidd J, Kidd K, Khakoo SI, Alexander G, Goedert JJ, Kirk GD, Donfield SM, Rosen HR, Tobler LH, Busch MP, McHutchison JG, Goldstein DB, Carrington M (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801PubMedCentralPubMed

159.

Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Chayama K, Nakamura Y, Kumada H (2010) 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 52:421–429PubMed

160.

Kurosaki M, Sakamoto N, Iwasaki M, Sakamoto M, Suzuki Y, Hiramatsu N, Sugauchi F, Yatsuhashi H, Izumi N (2011) Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis. J Gastroenterol 46:401–409PubMed

161.

Alestig E, Arnholm B, Eilard A, Lagging M, Nilsson S, Norkrans G, Wahlberg T, Wejstal R, Westin J, Lindh M (2011) Core mutations, IL28B polymorphisms and response to peginterferon/ribavirin treatment in Swedish patients with hepatitis C virus genotype 1 infection. BMC Infect Dis 11:124PubMedCentralPubMed

162.

Miura M, Maekawa S, Kadokura M, Sueki R, Komase K, Shindo H, Ohmori T, Kanayama A, Shindo K, Amemiya F, Nakayama Y, Kitamura T, Uetake T, Inoue T, Sakamoto M, Okada S, Enomoto N (2012) Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C. Hepatol Int 6(1):386–396

163.

Toyoda H, Kumada T, Hayashi K, Honda T, Katano Y, Goto H, Kawaguchi T, Murakami Y, Matsuda F (2011) Antiviral combination therapy with peginterferon and ribavirin does not induce a therapeutically resistant mutation in the HCV core region regardless of genetic polymorphism near the IL28B gene. J Med Virol 83:1559–1564PubMed

164.

Maekawa S, Sakamoto M, Miura M, Kadokura M, Sueki R, Komase K, Shindo H, Komatsu N, Shindo K, Kanayama A, Ohmori T, Amemiya F, Takano S, Yamaguchi T, Nakayama Y, Kitamura T, Inoue T, Okada S, Enomoto N (2012) Comprehensive analysis for viral elements and interleukin-28B polymorphisms in response to pegylated interferon plus ribavirin therapy in hepatitis C virus 1B infection. Hepatology 56(5):1611–1621

165.

Hayashi K, Katano Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Ishikawa T, Nakano I, Yoshioka K, Toyoda H, Kumada T, Goto H (2011) Association of interleukin 28B and mutations in the core and NS5A region of hepatitis C virus with response to peg-interferon and ribavirin therapy. Liver Int 31:1359–1365PubMed

166.

Hayashi K, Katano Y, Kuzuya T, Tachi Y, Honda T, Ishigami M, Itoh A, Hirooka Y, Ishikawa T, Nakano I, Urano F, Yoshioka K, Toyoda H, Kumada T, Goto H (2012) Prevalence of hepatitis C virus genotype 1a in Japan and correlation of mutations in the NS5A region and single-nucleotide polymorphism of interleukin-28B with the response to combination therapy with pegylated-interferon-alpha 2b and ribavirin. J Med Virol 84:438–444PubMed

167.

Hiraga N, Abe H, Imamura M, Tsuge M, Takahashi S, Hayes CN, Ochi H, Tateno C, Yoshizato K, Nakamura Y, Kamatani N, Chayama K (2011) Impact of viral amino acid substitutions and host interleukin-28b polymorphism on replication and susceptibility to interferon of hepatitis C virus. Hepatology 54:764–771PubMed

Title: Role of different regions of the hepatitis C virus genome in the therapeutic response to interferon-based treatment
Authors: Saba Khaliq
Noreen Latief
Shah Jahan
Publication date: 01-01-2014
Publisher: Springer Vienna
Published in: Archives of Virology / Issue 1/2014
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-013-1780-x

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