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Archives of Virology

, Volume 159, Issue 5, pp 849–862 | Cite as

The role of microRNAs in hepatitis C virus RNA replication

  • K. Dominik Conrad
  • Michael NiepmannEmail author
Brief Review

Abstract

Replication of hepatitis C virus (HCV) RNA is influenced by a variety of microRNAs, with the main player being the liver-specific microRNA-122 (miR-122). Binding of miR-122 to two binding sites near the 5′ end of the 5′ untranslated region (UTR) of the HCV genomic RNA results in at least two different effects. On the one hand, binding of miR-122 and the resulting recruitment of protein complexes containing Argonaute (Ago) proteins appears to mask the viral RNA′s 5′ end and stabilizes the viral RNA against nucleolytic degradation. On the other hand, this interaction of miR-122 with the 5′-UTR also stimulates HCV RNA translation directed by the internal ribosome entry site (IRES) located downstream of the miR-122 binding sites. However, it is suspected that additional, yet undefined roles of miR-122 in HCV replication may also contribute to HCV propagation. Accordingly, miR-122 is considered to contribute to the liver tropism of the virus. Besides miR-122, let-7b, miR-196, miR-199a* and miR-448 have also been reported to interact directly with the HCV RNA. However, the latter microRNAs inhibit HCV replication, and it has been speculated that miR-199a* contributes indirectly to HCV tissue tropism, since it is mostly expressed in cells other than hepatocytes. Other microRNAs influence HCV replication indirectly. Some of those are advantageous for HCV propagation, while others suppress HCV replication. Consequently, HCV up-regulates or down-regulates, respectively, the expression of most of these miRNAs.

Keywords

Internal Ribosome Entry Site Internal Ribosome Entry Site Element NS5B Code Region Seed Target Sequence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We apologize to those investigators whose work has not been discussed due to space limitations. Work in MN′s lab is supported by grants of the Deutsche Forschungsgemeinschaft, DFG (SFB 1021, IRTG 1384, Ni 604/2-2).

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Liu Y, Wimmer E, Paul AV (2009) Cis-acting RNA elements in human and animal plus-strand RNA viruses. Biochim Biophys Acta 1789:495–517PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Gosert R, Egger D, Lohmann V, Bartenschlager R, Blum HE, Bienz K, Moradpour D (2003) Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 77:5487–5492PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Moradpour D, Penin F (2013) Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol 369:113–142PubMedGoogle Scholar
  4. 4.
    Lohmann V (2013) Hepatitis C Virus RNA Replication. Curr Top Microbiol Immunol 369:167–198PubMedGoogle Scholar
  5. 5.
    Friebe P, Lohmann V, Krieger N, Bartenschlager R (2001) Sequences in the 5’ nontranslated region of hepatitis C virus required for RNA replication. J Virol 75:12047–12057PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Vassilaki N, Friebe P, Meuleman P, Kallis S, Kaul A, Paranhos-Baccala G, Leroux-Roels G, Mavromara P, Bartenschlager R (2008) Role of the hepatitis C virus core+1 open reading frame and core cis-acting RNA elements in viral RNA translation and replication. J Virol 82:11503–11515PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Niepmann M (2009) Internal translation initiation of picornaviruses and hepatitis C virus. Biochim Biophys Acta 1789:529–541PubMedCrossRefGoogle Scholar
  8. 8.
    Firth AE, Brierley I (2012) Non-canonical translation in RNA viruses. J Gen Virol 93:1385–1409PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Ito T, Tahara SM, Lai MM (1998) The 3’-untranslated region of hepatitis C virus RNA enhances translation from an internal ribosomal entry site. J Virol 72:8789–8796PubMedCentralPubMedGoogle Scholar
  10. 10.
    Song Y, Friebe P, Tzima E, Jünemann C, Bartenschlager R, Niepmann M (2006) The hepatitis C virus RNA 3’-untranslated region strongly enhances translation directed by the internal ribosome entry site. J Virol 80:11579–11588PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Bradrick SS, Walters RW, Gromeier M (2006) The hepatitis C virus 3’-untranslated region or a poly(A) tract promote efficient translation subsequent to the initiation phase. Nucleic Acids Res 34:1293–1303PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Bung C, Bochkaeva Z, Terenin I, Zinovkin R, Shatsky IN, Niepmann M (2010) Influence of the hepatitis C virus 3’-untranslated region on IRES-dependent and cap-dependent translation initiation. FEBS Lett 584:837–842PubMedCrossRefGoogle Scholar
  13. 13.
    Hoffman B, Liu Q (2011) Hepatitis C viral protein translation: mechanisms and implications in developing antivirals. Liver Int 31:1449–1467PubMedCrossRefGoogle Scholar
  14. 14.
    Niepmann M (2013) Hepatitis C virus RNA translation. Curr Top Microbiol Immunol 369:143–166PubMedGoogle Scholar
  15. 15.
    Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309:1577–1581PubMedCrossRefGoogle Scholar
  16. 16.
    Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T (2004) Identification of virus-encoded microRNAs. Science 304:734–736PubMedCrossRefGoogle Scholar
  17. 17.
    Czech B, Hannon GJ (2011) Small RNA sorting: matchmaking for Argonautes. Nat Rev Genet 12:19–31PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Huntzinger E, Izaurralde E (2011) Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet 12:99–110PubMedCrossRefGoogle Scholar
  19. 19.
    Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19:586–593PubMedCrossRefGoogle Scholar
  20. 20.
    Wang Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ (2008) Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 456:921–926PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Jinek M, Doudna JA (2009) A three-dimensional view of the molecular machinery of RNA interference. Nature 457:405–412PubMedCrossRefGoogle Scholar
  22. 22.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739PubMedCrossRefGoogle Scholar
  24. 24.
    Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, Xu C, Mason WS, Moloshok T, Bort R, Zaret KS, Taylor JM (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 1:106–113PubMedCrossRefGoogle Scholar
  25. 25.
    Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Fu H, Tie Y, Xu C, Zhang Z, Zhu J, Shi Y, Jiang H, Sun Z, Zheng X (2005) Identification of human fetal liver miRNAs by a novel method. FEBS Lett 579:3849–3854PubMedCrossRefGoogle Scholar
  27. 27.
    Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foa R, Schliwka J, Fuchs U, Novosel A, Muller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Jopling C (2012) Liver-specific microRNA-122: Biogenesis and function. RNA Biol 9:137–142PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Perrault M, Pecheur EI (2009) The hepatitis C virus and its hepatic environment: a toxic but finely tuned partnership. Biochem J 423:303–314PubMedCrossRefGoogle Scholar
  30. 30.
    Zeisel MB, Felmlee DJ, Baumert TF (2013) Hepatitis C virus entry. Curr Top Microbiol Immunol 369:87–112PubMedGoogle Scholar
  31. 31.
    Thibault PA, Wilson JA (2013) Targeting miRNAs to treat Hepatitis C Virus infections and liver pathology: Inhibiting the virus and altering the host. Pharmacol Res 75:48–59PubMedCrossRefGoogle Scholar
  32. 32.
    Jopling CL, Schütz S, Sarnow P (2008) Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4:77–85PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Wilson JA, Zhang C, Huys A, Richardson CD (2011) Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J Virol 85:2342–2350PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Machlin ES, Sarnow P, Sagan SM (2011) Masking the 5’ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex. Proc Natl Acad Sci USA 108:3193–3198PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Goergen D, Niepmann M (2012) Stimulation of Hepatitis C Virus RNA translation by microRNA-122 occurs under different conditions in vivo and in vitro. Virus Res 167:343–352PubMedCrossRefGoogle Scholar
  36. 36.
    Shimakami T, Yamane D, Welsch C, Hensley L, Jangra RK, Lemon SM (2012) Base Pairing between Hepatitis C Virus RNA and MicroRNA 122 3’ of Its Seed Sequence Is Essential for Genome Stabilization and Production of Infectious Virus. J Virol 86:7372–7383PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Wilkinson KA, Merino EJ, Weeks KM (2006) Selective 2’-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nature Protocols 1:1610–1616PubMedCrossRefGoogle Scholar
  38. 38.
    Pang PS, Pham EA, Elazar M, Patel SG, Eckart MR, Glenn JS (2011) Structural Map of a MicroRNA-122:HCV Complex. J Virol 86:1250–1254PubMedCrossRefGoogle Scholar
  39. 39.
    Mortimer SA, Doudna JA (2013) Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure. Nucleic Acids Res 41:4230–4240PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Henke JI, Goergen D, Zheng J, Song Y, Schüttler CG, Fehr C, Jünemann C, Niepmann M (2008) microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 27:3300–3310PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Roberts AP, Lewis AP, Jopling CL (2011) miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res 39:7716–7729PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ, Lemon SM (2012) Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA 109:941–946PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Jangra RK, Yi M, Lemon SM (2010) Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 84:6615–6625PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Narbus CM, Israelow B, Sourisseau M, Michta ML, Hopcraft SE, Zeiner GM, Evans MJ (2011) HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle. J Virol 85:12087–12092PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Chang J, Guo JT, Jiang D, Guo H, Taylor JM, Block TM (2008) Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J Virol 82:8215–8223PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE, Pfeffer S, Landthaler M, Landgraf P, Kan S, Lindenbach BD, Chien M, Weir DB, Russo JJ, Ju J, Brownstein MJ, Sheridan R, Sander C, Zavolan M, Tuschl T, Rice CM (2007) Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci USA 104:12884–12889PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Li YP, Gottwein JM, Scheel TK, Jensen TB, Bukh J (2011) MicroRNA-122 antagonism against hepatitis C virus genotypes 1-6 and reduced efficacy by host RNA insertion or mutations in the HCV 5’ UTR. Proc Natl Acad Sci USA 108:4991–4996PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Fukuhara T, Kambara H, Shiokawa M, Ono C, Katoh H, Morita E, Okuzaki D, Maehara Y, Koike K, Matsuura Y (2012) Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. J Virol 86:7918–7933PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Jünemann C, Song Y, Bassili G, Goergen D, Henke J, Niepmann M (2007) Picornavirus internal ribosome entry site elements can stimulate translation of upstream genes. J Biol Chem 282:132–141PubMedCrossRefGoogle Scholar
  51. 51.
    Niepmann M (2009) Activation of hepatitis C virus translation by a liver-specific microRNA. Cell Cycle 8:1473–1477PubMedCrossRefGoogle Scholar
  52. 52.
    Vasudevan S, Tong Y, Steitz JA (2007) Switching from repression to activation: microRNAs can up-regulate translation. Science 318:1931–1934PubMedCrossRefGoogle Scholar
  53. 53.
    Orom UA, Nielsen FC, Lund AH (2008) MicroRNA-10a binds the 5’UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460–471PubMedCrossRefGoogle Scholar
  54. 54.
    Fehr C, Conrad DK, Niepmann M (2012) Differential stimulation of Hepatitis C Virus RNA translation by microRNA-122 in different cell cycle phases. Cell Cycle 11:277–285PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Conrad KD, Giering F, Erfurth C, Neumann A, Fehr C, Meister G, Niepmann M (2013) MicroRNA-122 dependent binding of Ago2 protein to hepatitis C virus RNA is associated with enhanced RNA stability and translation stimulation. PloS ONE 8:e56272PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Babaylova E, Graifer D, Malygin A, Stahl J, Shatsky I, Karpova G (2009) Positioning of subdomain IIId and apical loop of domain II of the hepatitis C IRES on the human 40S ribosome. Nucleic Acids Res 37:1141–1151PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Spahn CM, Kieft JS, Grassucci RA, Penczek PA, Zhou K, Doudna JA, Frank J (2001) Hepatitis C virus IRES RNA-induced changes in the conformation of the 40s ribosomal subunit. Science 291:1959–1962PubMedCrossRefGoogle Scholar
  58. 58.
    Filbin ME, Kieft JS (2011) HCV IRES domain IIb affects the configuration of coding RNA in the 40S subunit’s decoding groove. RNA 17:1258–1273PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Villanueva RA, Jangra RK, Yi M, Pyles R, Bourne N, Lemon SM (2010) miR-122 does not modulate the elongation phase of hepatitis C virus RNA synthesis in isolated replicase complexes. Antiviral Res 88:119–123PubMedCrossRefGoogle Scholar
  60. 60.
    Li Y, Masaki T, Yamane D, McGivern DR, Lemon SM (2013) Competing and noncompeting activities of miR-122 and the 5’ exonuclease Xrn1 in regulation of hepatitis C virus replication. Proc Natl Acad Sci USA 110:1881–1886PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Berezhna SY, Supekova L, Sever MJ, Schultz PG, Deniz AA (2011) Dual regulation of hepatitis C viral RNA by cellular RNAi requires partitioning of Ago2 to lipid droplets and P-bodies. RNA 17:1831–1845PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Petri S, Dueck A, Lehmann G, Putz N, Rüdel S, Kremmer E, Meister G (2011) Increased siRNA duplex stability correlates with reduced off-target and elevated on-target effects. RNA 17:737–749PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Zhang C, Huys A, Thibault PA, Wilson JA (2012) Requirements for human Dicer and TRBP in microRNA-122 regulation of HCV translation and RNA abundance. Virology 433:479–488PubMedCrossRefGoogle Scholar
  64. 64.
    Bradrick SS, Nagyal S, Novatt H (2013) A miRNA-responsive cell-free translation system facilitates isolation of hepatitis C virus miRNP complexes. RNA 19:1159–1169PubMedCrossRefGoogle Scholar
  65. 65.
    Huys A, Thibault PA, Wilson JA (2013) Modulation of Hepatitis C Virus RNA Accumulation and Translation by DDX6 and miR-122 Are Mediated by Separate Mechanisms. PloS ONE 8:e67437PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Nasheri N, Singaravelu R, Goodmurphy M, Lyn RK, Pezacki JP (2011) Competing roles of microRNA-122 recognition elements in hepatitis C virus RNA. Virology 410:336–344PubMedCrossRefGoogle Scholar
  67. 67.
    Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W (2009) Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med 15:31–33PubMedCrossRefGoogle Scholar
  68. 68.
    Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198–201PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van der Meer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR (2013) Treatment of HCV infection by targeting microRNA. N Engl J Med 368:1685–1694PubMedCrossRefGoogle Scholar
  70. 70.
    Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M (2005) Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438:685–689PubMedCrossRefGoogle Scholar
  71. 71.
    Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98PubMedCrossRefGoogle Scholar
  72. 72.
    Jiang J, Luo G (2009) Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J Virol 83:12680–12691PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Coller KE, Heaton NS, Berger KL, Cooper JD, Saunders JL, Randall G (2012) Molecular determinants and dynamics of hepatitis C virus secretion. PLoS Pathog 8:e1002466PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Lindenbach BD (2013) Viron Assembly and Release. Curr Top Microbiol Immunol 369:199–218PubMedCentralPubMedGoogle Scholar
  75. 75.
    Frentzen A, Kusuma A, Guerlevik E, Hueging K, Knocke S, Ginkel C, Brown RJ, Heim M, Dill MT, Kroger A, Kalinke U, Kaderali L, Kuehnel F, Pietschmann T (2013) Cell entry, efficient RNA replication, and production of infectious hepatitis C virus progeny in mouse liver-derived cells. Hepatology. doi: 10.1002/hep.26626. [Epub ahead of print]
  76. 76.
    Wen J, Friedman JR (2012) miR-122 regulates hepatic lipid metabolism and tumor suppression. J Clin Invest 122:2773–2776PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Szabo G, Bala S (2013) MicroRNAs in liver disease. Nat Rev Gastroenterol Hepatol. doi: 10.1038/nrgastro201387 [Epub ahead of print]
  78. 78.
    Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP (2012) MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J Clin Invest 122:2884–2897PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    van der Meer AJ, Farid WR, Sonneveld MJ, de Ruiter PE, Boonstra A, van Vuuren AJ, Verheij J, Hansen BE, de Knegt RJ, van der Laan LJ, Janssen HL (2013) Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat 20:158–166PubMedCrossRefGoogle Scholar
  80. 80.
    Köberle V, Waidmann O, Kronenberger B, Andrei A, Susser S, Füller C, Perner D, Zeuzem S, Sarrazin C, Piiper A (2013) Serum microRNA-122 kinetics in patients with chronic hepatitis C virus infection during antiviral therapy. J Viral Hepat 20:530–535PubMedCrossRefGoogle Scholar
  81. 81.
    Murakami Y, Aly HH, Tajima A, Inoue I, Shimotohno K (2009) Regulation of the hepatitis C virus genome replication by miR-199a*. J Hepatol 50:453–460PubMedCrossRefGoogle Scholar
  82. 82.
    Pietschmann T (2009) Regulation of hepatitis C virus replication by microRNAs. J Hepatol 50:441–444PubMedCrossRefGoogle Scholar
  83. 83.
    Liang Y, Ridzon D, Wong L, Chen C (2007) Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8:166PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Andre P, Perlemuter G, Budkowska A, Brechot C, Lotteau V (2005) Hepatitis C virus particles and lipoprotein metabolism. Semin Liver Dis 25:93–104PubMedCrossRefGoogle Scholar
  85. 85.
    Poumbourios P, Drummer HE (2007) Recent advances in our understanding of receptor binding, viral fusion and cell entry of hepatitis C virus: new targets for the design of antiviral agents. Antivir Chem Chemother 18:169–189PubMedGoogle Scholar
  86. 86.
    Cheng JC, Yeh YJ, Tseng CP, Hsu SD, Chang YL, Sakamoto N, Huang HD (2012) Let-7b is a novel regulator of hepatitis C virus replication. Cell Mol Life Sci 69:2621–2633PubMedCrossRefGoogle Scholar
  87. 87.
    Hou W, Tian Q, Zheng J, Bonkovsky HL (2010) MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins. Hepatology 51:1494–1504PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Bruni R, Marcantonio C, Tritarelli E, Tataseo P, Stellacci E, Costantino A, Villano U, Battistini A, Ciccaglione AR (2011) An integrated approach identifies IFN-regulated microRNAs and targeted mRNAs modulated by different HCV replicon clones. BMC Genomics 12:485PubMedCentralPubMedCrossRefGoogle Scholar
  89. 89.
    Liu X, Wang T, Wakita T, Yang W (2010) Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology 398:57–67PubMedCrossRefGoogle Scholar
  90. 90.
    Ishida H, Tatsumi T, Hosui A, Nawa T, Kodama T, Shimizu S, Hikita H, Hiramatsu N, Kanto T, Hayashi N, Takehara T (2011) Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway. Biochem Biophys Res Commun 412:92–97PubMedCrossRefGoogle Scholar
  91. 91.
    Hoffmann TW, Duverlie G, Bengrine A (2012) MicroRNAs and hepatitis C virus: toward the end of miR-122 supremacy. Virol J 9:109PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Shwetha S, Gouthamchandra K, Chandra M, Ravishankar B, Khaja MN, Das S (2013) Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis. Sci Rep 3:1555PubMedCentralPubMedCrossRefGoogle Scholar
  93. 93.
    Ura S, Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Sunakozaka H, Sakai Y, Horimoto K, Kaneko S (2009) Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology 49:1098–1112PubMedCrossRefGoogle Scholar
  94. 94.
    Marquez RT, Wendlandt E, Galle CS, Keck K, McCaffrey AP (2010) MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-kappaB signaling. Am J Physiol Gastrointest Liver Physiol 298:G535–G541PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Chen Y, Chen J, Wang H, Shi J, Wu K, Liu S, Liu Y, Wu J (2013) HCV-Induced miR-21 Contributes to Evasion of Host Immune System by Targeting MyD88 and IRAK1. PLoS Pathogens 9:e1003248PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Bhanja Chowdhury J, Shrivastava S, Steele R, Di Bisceglie AM, Ray R, Ray RB (2012) Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. J Virol 86:10221–10225PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Zhang X, Daucher M, Armistead D, Russell R, Kottilil S (2013) MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-alpha. PLoS ONE 8:e55733PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Singaravelu R, Chen R, Lyn RK, Jones DM, O’Hara S, Rouleau Y, Cheng J, Srinivasan P, Nasheri N, Russell RS, Lorne D, Pezacki JP (2013) Hepatitis C virus induced up-regulation of microRNA-27: A novel mechanism for hepatic steatosis. Hepatology. doi: 10.1002/hep.26634. [Epub ahead of print]
  99. 99.
    Bandyopadhyay S, Friedman RC, Marquez RT, Keck K, Kong B, Icardi MS, Brown KE, Burge CB, Schmidt WN, Wang Y, McCaffrey AP (2011) Hepatitis C virus infection and hepatic stellate cell activation downregulate miR-29: miR-29 overexpression reduces hepatitis C viral abundance in culture. J Infect Dis 203:1753–1762PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Shirasaki T, Honda M, Shimakami T, Horii R, Yamashita T, Sakai Y, Sakai A, Okada H, Watanabe R, Murakami S, Yi M, Lemon SM, Kaneko S (2013) MicroRNA-27a regulates lipid metabolism and inhibits hepatitis C virus replication in human hepatoma cells. J Virol 87:5270–5286PubMedCentralPubMedCrossRefGoogle Scholar
  101. 101.
    Steuerwald NM, Parsons JC, Bennett K, Bates TC, Bonkovsky HL (2010) Parallel microRNA and mRNA expression profiling of (genotype 1b) human hepatoma cells expressing hepatitis C virus. Liver Int 30:1490–1504PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Institute of Biochemistry, School of MedicineJustus-Liebig-UniversityGiessenGermany

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