1932

Abstract

Many viruses encode or subvert cellular microRNAs (miRNAs) to aid in their gene expression, amplification strategies, or pathogenic signatures. miRNAs typically downregulate gene expression by binding to the 3′ untranslated region of their mRNA targets. As a result, target mRNAs are translationally repressed and subsequently deadenylated and degraded. Curiously, hepatitis C virus (HCV), a member of the family, recruits two molecules of liver-specific microRNA-122 (miR-122) to the 5′ end of its genome. In contrast to the canonical activity of miRNAs, the interactions of miR-122 with the viral genome promote viral RNA accumulation in cultured cells and in animal models of HCV infection. Sequestration of miR-122 results in loss of viral RNA both in cell culture and in the livers of chronic HCV-infected patients. This review discusses the mechanisms by which miR-122 is thought to enhance viral RNA abundance and the consequences of miR-122–HCV interactions. We also describe preliminary findings from phase II clinical trials in patients treated with miR-122 antisense oligonucleotides.

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2016-09-29
2024-04-18
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Literature Cited

  1. Fabian MR, Sonenberg N. 1.  2012. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat. Struct. Mol. Biol. 19:586–93 [Google Scholar]
  2. Fabian MR, Sonenberg N, Filipowicz W. 2.  2010. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem. 79:351–79 [Google Scholar]
  3. Friedman RC, Farh KK, Burge CB, Bartel DP. 3.  2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105 [Google Scholar]
  4. Ha M, Kim VN. 4.  2014. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15:509–24 [Google Scholar]
  5. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. 5.  2002. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 21:4663–70 [Google Scholar]
  6. Monteys AM, Spengler RM, Wan J, Tecedor L, Lennox KA. 6.  et al. 2010. Structure and activity of putative intronic miRNA promoters. RNA 16:495–505 [Google Scholar]
  7. Ozsolak F, Poling LL, Wang Z, Liu H, Liu XS. 7.  et al. 2008. Chromatin structure analyses identify miRNA promoters. Genes Dev 22:3172–83 [Google Scholar]
  8. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. 8.  2004. Processing of primary microRNAs by the Microprocessor complex. Nature 432:231–35 [Google Scholar]
  9. Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B. 9.  et al. 2004. The Microprocessor complex mediates the genesis of microRNAs. Nature 432:235–40 [Google Scholar]
  10. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. 10.  2004. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18:3016–27 [Google Scholar]
  11. Landthaler M, Yalcin A, Tuschl T. 11.  2004. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr. Biol. 14:2162–67 [Google Scholar]
  12. Lee Y, Ahn C, Han J, Choi H, Kim J. 12.  et al. 2003. The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–19 [Google Scholar]
  13. Bohnsack MT, Czaplinski K, Gorlich D. 13.  2004. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 10:185–91 [Google Scholar]
  14. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. 14.  2004. Nuclear export of microRNA precursors. Science 303:95–98 [Google Scholar]
  15. Yi R, Qin Y, Macara IG, Cullen BR. 15.  2003. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–16 [Google Scholar]
  16. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. 16.  2001. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409:363–66 [Google Scholar]
  17. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S. 17.  et al. 2001. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23–34 [Google Scholar]
  18. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. 18.  2001. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 293:834–38 [Google Scholar]
  19. Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. 19.  2001. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 15:2654–59 [Google Scholar]
  20. Knight SW, Bass BL. 20.  2001. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269–71 [Google Scholar]
  21. Lee HY, Zhou K, Smith AM, Noland CL, Doudna JA. 21.  2013. Differential roles of human Dicer-binding proteins TRBP and PACT in small RNA processing. Nucleic Acids Res 41:6568–76 [Google Scholar]
  22. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. 22.  2001. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science 293:1146–50 [Google Scholar]
  23. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B. 23.  et al. 2002. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev 16:720–28 [Google Scholar]
  24. Chendrimada TP, Gregory RI, Kumaraswamy E, Norman J, Cooch N. 24.  et al. 2005. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436:740–44 [Google Scholar]
  25. Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. 25.  2005. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123:631–40 [Google Scholar]
  26. MacRae IJ, Ma E, Zhou M, Robinson CV, Doudna JA. 26.  2008. In vitro reconstitution of the human RISC-loading complex. PNAS 105:512–17 [Google Scholar]
  27. Maniataki E, Mourelatos Z. 27.  2005. A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. Genes Dev 19:2979–90 [Google Scholar]
  28. Betancur JG, Tomari Y. 28.  2012. Dicer is dispensable for asymmetric RISC loading in mammals. RNA 18:24–30 [Google Scholar]
  29. Kawamata T, Seitz H, Tomari Y. 29.  2009. Structural determinants of miRNAs for RISC loading and slicer-independent unwinding. Nat. Struct. Mol. Biol. 16:953–60 [Google Scholar]
  30. Kawamata T, Tomari Y. 30.  2010. Making RISC. Trends Biochem. Sci. 35:368–76 [Google Scholar]
  31. Ye X, Huang N, Liu Y, Paroo Z, Huerta C. 31.  et al. 2011. Structure of C3PO and mechanism of human RISC activation. Nat. Struct. Mol. Biol. 18:650–57 [Google Scholar]
  32. Yoda M, Kawamata T, Paroo Z, Ye X, Iwasaki S. 32.  et al. 2010. ATP-dependent human RISC assembly pathways. Nat. Struct. Mol. Biol. 17:17–23 [Google Scholar]
  33. Khvorova A, Reynolds A, Jayasena SD. 33.  2003. Functional siRNAs and miRNAs exhibit strand bias. Cell 115:209–16 [Google Scholar]
  34. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. 34.  2003. Asymmetry in the assembly of the RNAi enzyme complex. Cell 115:199–208 [Google Scholar]
  35. Liu J, Carmell MA, Rivas FV, Marsden CG, Thomson JM. 35.  et al. 2004. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–41 [Google Scholar]
  36. Brengues M, Teixeira D, Parker R. 36.  2005. Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310:486–89 [Google Scholar]
  37. Bagga S, Bracht J, Hunter S, Massirer K, Holtz J. 37.  et al. 2005. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122:553–63 [Google Scholar]
  38. Azuma-Mukai A, Oguri H, Mituyama T, Qian ZR, Asai K. 38.  et al. 2008. Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing. PNAS 105:7964–69 [Google Scholar]
  39. Dueck A, Ziegler C, Eichner A, Berezikov E, Meister G. 39.  2012. microRNAs associated with the different human Argonaute proteins. Nucleic Acids Res 40:9850–62 [Google Scholar]
  40. Su H, Trombly MI, Chen J, Wang X. 40.  2009. Essential and overlapping functions for mammalian Argonautes in microRNA silencing. Genes Dev 23:304–17 [Google Scholar]
  41. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. 41.  2004. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol. Cell 15:185–97 [Google Scholar]
  42. Bartel DP. 42.  2009. MicroRNAs: Target recognition and regulatory functions. Cell 136:215–33 [Google Scholar]
  43. Humphreys DT, Westman BJ, Martin DI, Preiss T. 43.  2005. MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. PNAS 102:16961–66 [Google Scholar]
  44. Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L. 44.  et al. 2007. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science 317:1764–67 [Google Scholar]
  45. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N. 45.  et al. 2005. Inhibition of translational initiation by let-7 microRNA in human cells. Science 309:1573–76 [Google Scholar]
  46. Wang B, Yanez A, Novina CD. 46.  2008. MicroRNA-repressed mRNAs contain 40S but not 60S components. PNAS 105:5343–48 [Google Scholar]
  47. Nottrott S, Simard MJ, Richter JD. 47.  2006. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat. Struct. Mol. Biol. 13:1108–14 [Google Scholar]
  48. Maroney PA, Yu Y, Fisher J, Nilsen TW. 48.  2006. Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat. Struct. Mol. Biol. 13:1102–7 [Google Scholar]
  49. Olsen PH, Ambros V. 49.  1999. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev. Biol. 216:671–80 [Google Scholar]
  50. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA. 50.  2006. Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21:533–42 [Google Scholar]
  51. Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P, Izaurralde E. 51.  2006. mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 20:1885–98 [Google Scholar]
  52. Chen CY, Zheng D, Xia Z, Shyu AB. 52.  2009. Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps. Nat. Struct. Mol. Biol. 16:1160–66 [Google Scholar]
  53. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S. 53.  et al. 2006. Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312:75–79 [Google Scholar]
  54. Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E. 54.  2005. A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11:1640–47 [Google Scholar]
  55. Wu L, Fan J, Belasco JG. 55.  2006. MicroRNAs direct rapid deadenylation of mRNA. PNAS 103:4034–39 [Google Scholar]
  56. Huntzinger E, Kuzuoglu-Ozturk D, Braun JE, Eulalio A, Wohlbold L, Izaurralde E. 56.  2013. The interactions of GW182 proteins with PABP and deadenylases are required for both translational repression and degradation of miRNA targets. Nucleic Acids Res 41:978–94 [Google Scholar]
  57. Braun JE, Huntzinger E, Fauser M, Izaurralde E. 57.  2011. GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets. Mol. Cell 44:120–33 [Google Scholar]
  58. Chekulaeva M, Mathys H, Zipprich JT, Attig J, Colic M. 58.  et al. 2011. miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs. Nat. Struct. Mol. Biol. 18:1218–26 [Google Scholar]
  59. Fabian MR, Cieplak MK, Frank F, Morita M, Green J. 59.  et al. 2011. miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT. Nat. Struct. Mol. Biol. 18:1211–17 [Google Scholar]
  60. Wahle E, Winkler GS. 60.  2013. RNA decay machines: deadenylation by the Ccr4–Not and Pan2–Pan3 complexes. Biochim. Biophys. Acta 1829:561–70 [Google Scholar]
  61. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. 61.  2002. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12:735–39 [Google Scholar]
  62. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E. 62.  et al. 2005. MicroRNA expression in zebrafish embryonic development. Science 309:310–11 [Google Scholar]
  63. Chang J, Nicolas E, Marks D, Sander C, Lerro A. 63.  et al. 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 1:106–13 [Google Scholar]
  64. Li ZY, Xi Y, Zhu WN, Zeng C, Zhang ZQ. 64.  et al. 2011. Positive regulation of hepatic miR-122 expression by HNF4α. J. Hepatol. 55:602–11 [Google Scholar]
  65. Dhir A, Dhir S, Proudfoot NJ, Jopling CL. 65.  2015. Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nat. Struct. Mol. Biol. 22:319–27 [Google Scholar]
  66. Odom DT, Dowell RD, Jacobsen ES, Nekludova L, Rolfe PA. 66.  et al. 2006. Core transcriptional regulatory circuitry in human hepatocytes. Mol. Syst. Biol. 2:2006.0017 [Google Scholar]
  67. Gatfield D, Le Martelot G, Vejnar CE, Gerlach D, Schaad O. 67.  et al. 2009. Integration of microRNA miR-122 in hepatic circadian gene expression. Genes Dev 23:1313–26 [Google Scholar]
  68. Katoh T, Sakaguchi Y, Miyauchi K, Suzuki T, Kashiwabara S. 68.  et al. 2009. Selective stabilization of mammalian microRNAs by 3′ adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2. Genes Dev 23:433–38 [Google Scholar]
  69. Perumal K, Reddy R. 69.  2002. The 3′ end formation in small RNAs. Gene Expr 10:59–78 [Google Scholar]
  70. Burroughs AM, Ando Y, de Hoon MJ, Tomaru Y, Nishibu T. 70.  et al. 2010. A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness. Genome Res 20:1398–410 [Google Scholar]
  71. Burns DM, D'Ambrogio A, Nottrott S, Richter JD. 71.  2011. CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation. Nature 473:105–8 [Google Scholar]
  72. Katoh T, Hojo H, Suzuki T. 72.  2015. Destabilization of microRNAs in human cells by 3′ deadenylation mediated by PARN and CUGBP1. Nucleic Acids Res 43:7521–34 [Google Scholar]
  73. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. 73.  2006. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125:1111–24 [Google Scholar]
  74. Teixeira D, Sheth U, Valencia-Sanchez MA, Brengues M, Parker R. 74.  2005. Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA 11:371–82 [Google Scholar]
  75. Arribere JA, Doudna JA, Gilbert WV. 75.  2011. Reconsidering movement of eukaryotic mRNAs between polysomes and P bodies. Mol. Cell 44:745–58 [Google Scholar]
  76. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T. 76.  et al. 2005. Silencing of microRNAs in vivo with “antagomirs.”. Nature 438:685–89 [Google Scholar]
  77. Esau C, Davis S, Murray SF, Yu XX, Pandey SK. 77.  et al. 2006. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 3:87–98 [Google Scholar]
  78. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A. 78.  et al. 2008. LNA-mediated microRNA silencing in non-human primates. Nature 452:896–99 [Google Scholar]
  79. Elmen J, Lindow M, Silahtaroglu A, Bak M, Christensen M. 79.  et al. 2008. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res 36:1153–62 [Google Scholar]
  80. Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ. 80.  et al. 2012. MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. J. Clin. Investig. 122:2884–97 [Google Scholar]
  81. Castoldi M, Vujic Spasic M, Altamura S, Elmen J, Lindow M. 81.  et al. 2011. The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice. J. Clin. Investig. 121:1386–96 [Google Scholar]
  82. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. 82.  2009. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28:3526–36 [Google Scholar]
  83. Kutay H, Bai S, Datta J, Motiwala T, Pogribny I. 83.  et al. 2006. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J. Cell Biochem. 99:671–78 [Google Scholar]
  84. Bai S, Nasser MW, Wang B, Hsu SH, Datta J. 84.  et al. 2009. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J. Biol. Chem. 284:32015–27 [Google Scholar]
  85. Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW. 85.  et al. 2009. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 49:1571–82 [Google Scholar]
  86. Luna JM, Scheel TK, Danino T, Shaw KS, Mele A. 86.  et al. 2015. Hepatitis C virus RNA functionally sequesters miR-122. Cell 160:1099–110 [Google Scholar]
  87. Spaniel C, Honda M, Selitsky SR, Yamane D, Shimakami T. 87.  et al. 2013. MicroRNA-122 abundance in hepatocellular carcinoma and non-tumor liver tissue from Japanese patients with persistent HCV versus HBV infection. PLOS ONE 8:e76867 [Google Scholar]
  88. Hoofnagle JH. 88.  2002. Course and outcome of hepatitis C. Hepatology 36:S21–29 [Google Scholar]
  89. Lavanchy D. 89.  2011. Evolving epidemiology of hepatitis C virus. Clin. Microbiol. Infect. 17:107–15 [Google Scholar]
  90. Rice CM, Saeed M. 90.  2014. Hepatitis C: Treatment triumphs. Nature 510:43–44 [Google Scholar]
  91. Lindenbach BD, Rice CM. 91.  2013. The ins and outs of hepatitis C virus entry and assembly. Nat. Rev. Microbiol. 11:688–700 [Google Scholar]
  92. Sagan SM, Chahal J, Sarnow P. 92.  2015. cis-Acting RNA elements in the hepatitis C virus RNA genome. Virus Res 206:90–98 [Google Scholar]
  93. Leuschner PJ, Ameres SL, Kueng S, Martinez J. 93.  2006. Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Rep 7:314–20 [Google Scholar]
  94. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A. 94.  et al. 2006. 5′-Triphosphate RNA is the ligand for RIG-I. Science 314:994–97 [Google Scholar]
  95. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T. 95.  et al. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5:730–37 [Google Scholar]
  96. Foy E, Li K, Sumpter R Jr, Loo YM, Johnson CL. 96.  et al. 2005. Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. PNAS 102:2986–91 [Google Scholar]
  97. Li K, Foy E, Ferreon JC, Nakamura M, Ferreon AC. 97.  et al. 2005. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. PNAS 102:2992–97 [Google Scholar]
  98. Sumpter R Jr, Loo YM, Foy E, Li K, Yoneyama M. 98.  et al. 2005. Regulating intracellular antiviral defense and permissiveness to hepatitis C virus RNA replication through a cellular RNA helicase, RIG-I. J. Virol. 79:2689–99 [Google Scholar]
  99. Wakita T, Pietschmann T, Kato T, Date T, Miyamoto M. 99.  et al. 2005. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med. 11:791–96 [Google Scholar]
  100. Zhong J, Gastaminza P, Cheng G, Kapadia S, Kato T. 100.  et al. 2005. Robust hepatitis C virus infection in vitro. PNAS 102:9294–99 [Google Scholar]
  101. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. 101.  2005. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 309:1577–81 [Google Scholar]
  102. Jopling CL, Schutz S, Sarnow P. 102.  2008. Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell Host Microbe 4:77–85 [Google Scholar]
  103. Jangra RK, Yi M, Lemon SM. 103.  2010. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J. Virol. 84:6615–25 [Google Scholar]
  104. Machlin ES, Sarnow P, Sagan SM. 104.  2011. Masking the 5′ terminal nucleotides of the hepatitis C virus genome by an unconventional microRNA-target RNA complex. PNAS 108:3193–98 [Google Scholar]
  105. Pang PS, Pham EA, Elazar M, Patel SG, Eckart MR, Glenn JS. 105.  2012. Structural map of a microRNA-122: hepatitis C virus complex. J. Virol. 86:1250–54 [Google Scholar]
  106. Mortimer SA, Doudna JA. 106.  2013. Unconventional miR-122 binding stabilizes the HCV genome by forming a trimolecular RNA structure. Nucleic Acids Res 41:4230–40 [Google Scholar]
  107. Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE. 107.  et al. 2007. Cellular cofactors affecting hepatitis C virus infection and replication. PNAS 104:12884–89 [Google Scholar]
  108. Wilson JA, Zhang C, Huys A, Richardson CD. 108.  2011. Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. J. Virol. 85:2342–50 [Google Scholar]
  109. Zhang C, Huys A, Thibault PA, Wilson JA. 109.  2012. Requirements for human Dicer and TRBP in microRNA-122 regulation of HCV translation and RNA abundance. Virology 433:479–88 [Google Scholar]
  110. Conrad KD, Giering F, Erfurth C, Neumann A, Fehr C. 110.  et al. 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:e56272 [Google Scholar]
  111. Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C. 111.  et al. 2012. Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. PNAS 109:941–46 [Google Scholar]
  112. Berezhna SY, Supekova L, Sever MJ, Schultz PG, Deniz AA. 112.  2011. Dual regulation of hepatitis C viral RNA by cellular RNAi requires partitioning of Ago2 to lipid droplets and P-bodies. RNA 17:1831–45 [Google Scholar]
  113. Scheller N, Mina LB, Galao RP, Chari A, Gimenez-Barcons M. 113.  et al. 2009. Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates. PNAS 106:13517–22 [Google Scholar]
  114. Jangra RK, Yi M, Lemon SM. 114.  2010. DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation. J. Virol. 84:6810–24 [Google Scholar]
  115. Ariumi Y, Kuroki M, Kushima Y, Osugi K, Hijikata M. 115.  et al. 2011. Hepatitis C virus hijacks P-body and stress granule components around lipid droplets. J. Virol. 85:6882–92 [Google Scholar]
  116. Huys A, Thibault PA, Wilson JA. 116.  2013. Modulation of hepatitis C virus RNA accumulation and translation by DDX6 and miR-122 are mediated by separate mechanisms. PLOS ONE 8:e67437 [Google Scholar]
  117. Pager CT, Schutz S, Abraham TM, Luo G, Sarnow P. 117.  2013. Modulation of hepatitis C virus RNA abundance and virus release by dispersion of processing bodies and enrichment of stress granules. Virology 435:472–84 [Google Scholar]
  118. Roberts AP, Doidge R, Tarr AW, Jopling CL. 118.  2014. The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by microRNA-122. Nucleic Acids Res 42:1257–69 [Google Scholar]
  119. Ingelfinger D, Arndt-Jovin DJ, Luhrmann R, Achsel T. 119.  2002. The human LSm1-7 proteins colocalize with the mRNA-degrading enzymes Dcp1/2 and Xrnl in distinct cytoplasmic foci. RNA 8:1489–501 [Google Scholar]
  120. Tharun S, He W, Mayes AE, Lennertz P, Beggs JD, Parker R. 120.  2000. Yeast Sm-like proteins function in mRNA decapping and decay. Nature 404:515–18 [Google Scholar]
  121. Tharun S, Parker R. 121.  2001. Targeting an mRNA for decapping: displacement of translation factors and association of the Lsm1p–7p complex on deadenylated yeast mRNAs. Mol. Cell 8:1075–83 [Google Scholar]
  122. He W, Parker R. 122.  2001. The yeast cytoplasmic LsmI/Pat1p complex protects mRNA 3′ termini from partial degradation. Genetics 158:1445–55 [Google Scholar]
  123. Cox EM, Sagan SM, Mortimer SA, Doudna JA, Sarnow P. 123.  2013. Enhancement of hepatitis C viral RNA abundance by precursor miR-122 molecules. RNA 19:1825–32 [Google Scholar]
  124. Henke JI, Goergen D, Zheng J, Song Y, Schuttler CG. 124.  et al. 2008. microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J 27:3300–10 [Google Scholar]
  125. Ricci EP, Limousin T, Soto-Rifo R, Allison R, Poyry T. 125.  et al. 2011. Activation of a microRNA response in trans reveals a new role for poly(A) in translational repression. Nucleic Acids Res 39:5215–31 [Google Scholar]
  126. Roberts AP, Lewis AP, Jopling CL. 126.  2011. miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res 39:7716–29 [Google Scholar]
  127. Diaz-Toledano R, Ariza-Mateos A, Birk A, Martinez-Garcia B, Gomez J. 127.  2009. In vitro characterization of a miR-122-sensitive double-helical switch element in the 5′ region of hepatitis C virus RNA. Nucleic Acids Res 37:5498–510 [Google Scholar]
  128. Li Y, Masaki T, Yamane D, McGivern DR, Lemon SM. 128.  2013. Competing and noncompeting activities of miR-122 and the 5′ exonuclease Xrn1 in regulation of hepatitis C virus replication. PNAS 110:1881–86 [Google Scholar]
  129. Thibault PA, Huys A, Amador-Canizares Y, Gailius JE, Pinel DE, Wilson JA. 129.  2015. Regulation of hepatitis C virus genome replication by Xrn1 and microRNA-122 binding to individual sites in the 5′ untranslated region. J. Virol. 89:6294–311 [Google Scholar]
  130. Sedano CD, Sarnow P. 130.  2014. Hepatitis C virus subverts liver-specific miR-122 to protect the viral genome from exoribonuclease Xrn2. Cell Host Microbe 16:257–64 [Google Scholar]
  131. Li Y, Yamane D, Lemon SM. 131.  2015. Dissecting the roles of the 5′ exoribonucleases Xrn1 and Xrn2 in restricting hepatitis C virus replication. J. Virol. 89:4857–65 [Google Scholar]
  132. Masaki T, Arend KC, Li Y, Yamane D, McGivern DR. 132.  et al. 2015. miR-122 stimulates hepatitis C virus RNA synthesis by altering the balance of viral RNAs engaged in replication versus translation. Cell Host Microbe 17:217–28 [Google Scholar]
  133. Li Y, Masaki T, Shimakami T, Lemon SM. 133.  2014. hnRNP L and NF90 interact with hepatitis C virus 5′-terminal untranslated RNA and promote efficient replication. J. Virol. 88:7199–209 [Google Scholar]
  134. Fukushi S, Okada M, Kageyama T, Hoshino FB, Nagai K, Katayama K. 134.  2001. Interaction of poly(rC)-binding protein 2 with the 5′-terminal stem loop of the hepatitis C virus genome. Virus Res 73:67–79 [Google Scholar]
  135. Wang L, Jeng KS, Lai MM. 135.  2011. Poly(C)-binding protein 2 interacts with sequences required for viral replication in the hepatitis C virus (HCV) 5′ untranslated region and directs HCV RNA replication through circularizing the viral genome. J. Virol. 85:7954–64 [Google Scholar]
  136. Israelow B, Mullokandov G, Agudo J, Sourisseau M, Bashir A. 136.  et al. 2014. Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors. Nat. Commun. 5:5408 [Google Scholar]
  137. Li YP, Gottwein JM, Scheel TK, Jensen TB, Bukh J. 137.  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. PNAS 108:4991–96 [Google Scholar]
  138. Thibault PA, Huys A, Dhillon P, Wilson JA. 138.  2013. MicroRNA-122-dependent and -independent replication of hepatitis C virus in Hep3B human hepatoma cells. Virology 436:179–90 [Google Scholar]
  139. Narbus CM, Israelow B, Sourisseau M, Michta ML, Hopcraft SE. 139.  et al. 2011. HepG2 cells expressing microRNA miR-122 support the entire hepatitis C virus life cycle. J. Virol. 85:12087–92 [Google Scholar]
  140. Ottosen S, Parsley TB, Yang L, Zeh K, van Doorn LJ. 140.  et al. 2015. In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122. Antimicrob. Agents Chemother. 59:599–608 [Google Scholar]
  141. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M. 141.  et al. 2013. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368:1685–94 [Google Scholar]
  142. Papenfort K, Podkaminski D, Hinton JC, Vogel J. 142.  2012. The ancestral SgrS RNA discriminates horizontally acquired Salmonella mRNAs through a single G-U wobble pair. PNAS 109:E757–64 [Google Scholar]
  143. Simmonds P. 143.  2013. The origin of hepatitis C virus. Curr. Top. Microbiol. Immunol. 369:1–15 [Google Scholar]
  144. Simons JN, Pilot-Matias TJ, Leary TP, Dawson GJ, Desai SM. 144.  et al. 1995. Identification of two flavivirus-like genomes in the GB hepatitis agent. PNAS 92:3401–5 [Google Scholar]
  145. Stapleton JT, Foung S, Muerhoff AS, Bukh J, Simmonds P. 145.  2011. The GB viruses: a review and proposed classification of GBV-A, GBV-C (HGV), and GBV-D in genus Pegivirus within the family Flaviviridae. J. Gen. Virol. 92:233–46 [Google Scholar]
  146. De Tomassi A, Pizzuti M, Traboni C. 146.  2003. Hep3B human hepatoma cells support replication of the wild-type and a 5′-end deletion mutant GB virus B replicon. J. Virol. 77:11875–81 [Google Scholar]
  147. Iwasaki Y, Mori K, Ishii K, Maki N, Iijima S. 147.  et al. 2011. Long-term persistent GBV-B infection and development of a chronic and progressive hepatitis C–like disease in marmosets. Front. Microbiol. 2:240 [Google Scholar]
  148. Sagan SM, Sarnow P, Wilson JA. 148.  2013. Modulation of GB virus B RNA abundance by microRNA-122: dependence on and escape from microRNA-122 restriction. J. Virol. 87:7338–47 [Google Scholar]
  149. Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA. 149.  et al. 2012. Serology-enabled discovery of genetically diverse hepaciviruses in a new host. J. Virol. 86:6171–78 [Google Scholar]
  150. Kapoor A, Simmonds P, Gerold G, Qaisar N, Jain K. 150.  et al. 2011. Characterization of a canine homolog of hepatitis C virus. PNAS 108:11608–13 [Google Scholar]
  151. Drexler JF, Corman VM, Muller MA, Lukashev AN, Gmyl A. 151.  et al. 2013. Evidence for novel hepaciviruses in rodents. PLOS Pathog 9:e1003438 [Google Scholar]
  152. Kapoor A, Simmonds P, Scheel TK, Hjelle B, Cullen JM. 152.  et al. 2013. Identification of rodent homologs of hepatitis C virus and pegiviruses. mBio 4:e00216–13 [Google Scholar]
  153. Lauck M, Sibley SD, Lara J, Purdy MA, Khudyakov Y. 153.  et al. 2013. A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate. J. Virol. 87:8971–81 [Google Scholar]
  154. Quan PL, Firth C, Conte JM, Williams SH, Zambrana-Torrelio CM. 154.  et al. 2013. Bats are a major natural reservoir for hepaciviruses and pegiviruses. PNAS 110:8194–99 [Google Scholar]
  155. Scheel TK, Kapoor A, Nishiuchi E, Brock KV, Yu Y. 155.  et al. 2015. Characterization of nonprimate hepacivirus and construction of a functional molecular clone. PNAS 112:2192–97 [Google Scholar]
  156. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M. 156.  et al. 2010. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198–201 [Google Scholar]
  157. van der Ree MH, van der Meer AJ, de Bruijne J, Maan R, van Vliet A. 157.  et al. 2014. Long-term safety and efficacy of microRNA-targeted therapy in chronic hepatitis C patients. Antivir. Res. 111:53–59 [Google Scholar]
  158. Gebert LF, Rebhan MA, Crivelli SE, Denzler R, Stoffel M, Hall J. 158.  2014. Miravirsen (SPC3649) can inhibit the biogenesis of miR-122. Nucleic Acids Res 42:609–21 [Google Scholar]
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