1887

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Volume 98, Issue 7

microRNA modulates viral replication by targeting a homologue of mammalian Free

Abstract

MicroRNAs (miRNAs) are important regulators of biological processes, including host–virus interaction. This study investigated the involvement of miR-8-5p in host–virus interaction. flies and cells challenged with Drosophila C virus (DCV) were found to have lower miR-8-5p abundance compared to uninfected samples. Lowering miR-8-5p abundance by experimental inhibition of the miRNA led to an increase in viral accumulation, suggesting that the observed decrease in the miR-8-5p abundance during DCV infection enhances viral replication. miR-8-5p putative targets were identified and included , a transcription factor gene whose mammalian homologue is induced by various viruses through kinase activation. Increasing miR-8-5p abundance using miR-8-5p mimics resulted in a decrease in and GFP reporter levels. Furthermore, when the putative target in was mutated, addition of miR-8-5p mimics did not result in the same antagonistic effect on . These results show negative regulation of by miR-8-5p and suggest that an miRNA-mediated pathway is involved in regulation during viral infection. To analyse the role of during DCV infection, was knocked down in cells prior to DCV infection. Knockdown of decreased DCV replication, providing evidence that up-regulation that is concomitant with miR-8-5p down-regulation during DCV infection supports viral replication. These results highlight the role of miRNA in regulating the transcription factor gene and uncover a previously unrecognized mechanism by which is regulated during host–virus interaction.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): DCV , Dicistroviridae , Drosophila , host-virus interaction , insect virus , Jun , miRNA and miRNA*
© 2017 The Authors
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2017-07-01
2024-04-25
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References

  1. Jonas S, Izaurralde E. Towards a molecular understanding of microRNA-mediated gene silencing. Nat Rev Genet 2015; 16:421–433 [View Article][PubMed]
     [Google Scholar]
  2. Lee YS, Nakahara K, Pham JW, Kim K, He Z et al. Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 2004; 117:69–81 [View Article][PubMed]
     [Google Scholar]
  3. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432:231–235 [View Article][PubMed]
     [Google Scholar]
  4. Han J, Lee Y, Yeom KH, Kim YK, Jin H et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 2004; 18:3016–3027 [View Article][PubMed]
     [Google Scholar]
  5. Lee Y, Ahn C, Han J, Choi H, Kim J et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425:415–419 [View Article][PubMed]
     [Google Scholar]
  6. Kawamata T, Tomari Y. Making RISC. Trends Biochem Sci 2010; 35:368–376 [View Article][PubMed]
     [Google Scholar]
  7. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 2014; 15:509–524 [View Article][PubMed]
     [Google Scholar]
  8. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA–target recognition. PLoS Biol 2005; 3:e85e85 [View Article][PubMed]
     [Google Scholar]
  9. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L et al. Combinatorial microRNA target predictions. Nat Genet 2005; 37:495–500 [View Article][PubMed]
     [Google Scholar]
  10. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB. Prediction of mammalian microRNA targets. Cell 2003; 115:787–798 [View Article][PubMed]
     [Google Scholar]
  11. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136:215–233 [View Article][PubMed]
     [Google Scholar]
  12. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 2014; 42:D68–D73 [View Article][PubMed]
     [Google Scholar]
  13. Betel D, Koppal A, Agius P, Sander C, Leslie C. Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 2010; 11:R90 [View Article][PubMed]
     [Google Scholar]
  14. Enright AJ, John B, Gaul U, Tuschl T, Sander C et al. MicroRNA targets in Drosophila. Genome Biol 2003; 5:R1 [View Article][PubMed]
     [Google Scholar]
  15. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19:92–105 [View Article][PubMed]
     [Google Scholar]
  16. Cloonan N. Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery. Bioessays 2015; 37:379–388 [View Article][PubMed]
     [Google Scholar]
  17. Cullen BR. MicroRNAs as mediators of viral evasion of the immune system. Nat Immunol 2013; 14:205–210 [View Article][PubMed]
     [Google Scholar]
  18. Vidigal JA, Ventura A. The biological functions of miRNAs: lessons from in vivo studies. Trends Cell Biol 2015; 25:137–147 [View Article][PubMed]
     [Google Scholar]
  19. Sisk JM, Witwer KW, Tarwater PM, Clements JE. SIV replication is directly downregulated by four antiviral miRNAs. Retrovirology 2013; 10:95 [View Article][PubMed]
     [Google Scholar]
  20. Song L, Liu H, Gao S, Jiang W, Huang W. Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol 2010; 84:8849–8860 [View Article][PubMed]
     [Google Scholar]
  21. Forte E, Salinas RE, Chang C, Zhou T, Linnstaedt SD et al. The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells. J Virol 2012; 86:6889–6898 [View Article][PubMed]
     [Google Scholar]
  22. Jopling C. Liver-specific microRNA-122: biogenesis and function. RNA Biol 2012; 9:137–142 [View Article][PubMed]
     [Google Scholar]
  23. Randall G, Panis M, Cooper JD, Tellinghuisen TL, Sukhodolets KE et al. Cellular cofactors affecting hepatitis C virus infection and replication. Proc Natl Acad Sci USA 2007; 104:12884–12889 [View Article][PubMed]
     [Google Scholar]
  24. Zhou Y, Liu Y, Yan H, Li Y, Zhang H et al. miR-281, an abundant midgut-specific miRNA of the vector mosquito Aedes albopictus enhances dengue virus replication. Parasit Vectors 2014; 7:488 [View Article][PubMed]
     [Google Scholar]
  25. Asgari S. Regulatory role of cellular and viral microRNAs in insect–virus interactions. Curr Opin Insect Sci 2015; 8:104–110 [View Article]
     [Google Scholar]
  26. Guo YE, Steitz JA. Virus meets host microRNA: the destroyer, the booster, the hijacker. Mol Cell Biol 2014; 34:3780–3787 [View Article][PubMed]
     [Google Scholar]
  27. Scaria V, Jadhav V. microRNAs in viral oncogenesis. Retrovirology 2007; 4:82 [View Article][PubMed]
     [Google Scholar]
  28. Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annu Rev Microbiol 2010; 64:123–141 [View Article][PubMed]
     [Google Scholar]
  29. Umbach JL, Cullen BR. The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes Dev 2009; 23:1151–1164 [View Article][PubMed]
     [Google Scholar]
  30. Bier E, Guichard A. Deconstructing host-pathogen interactions in Drosophila. Dis Model Mech 2012; 5:48–61 [View Article][PubMed]
     [Google Scholar]
  31. Boutros M, Perrimon N. Drosophila genome takes flight. Nat Cell Biol 2000; 2:E53E54 [View Article][PubMed]
     [Google Scholar]
  32. Dionne MS, Schneider DS. Models of infectious diseases in the fruit fly Drosophila melanogaster. Dis Model Mech 2008; 1:43–49 [View Article][PubMed]
     [Google Scholar]
  33. Ferrandon D, Imler JL, Hetru C, Hoffmann JA. The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 2007; 7:862–874 [View Article][PubMed]
     [Google Scholar]
  34. Hughes TT, Allen AL, Bardin JE, Christian MN, Daimon K et al. Drosophila as a genetic model for studying pathogenic human viruses. Virology 2012; 423:1–5 [View Article][PubMed]
     [Google Scholar]
  35. Johnson KN, Christian PD. The novel genome organization of the insect picorna-like virus Drosophila C virus suggests this virus belongs to a previously undescribed virus family. J Gen Virol 1998; 79:191–203 [View Article][PubMed]
     [Google Scholar]
  36. Monsanto-Hearne V, Tham AL, Wong ZS, Asgari S, Johnson KN. Drosophila miR-956 suppression modulates Ectoderm-expressed 4 and inhibits viral replication. Virology 2017; 502:20–27 [View Article][PubMed]
     [Google Scholar]
  37. Singh CP, Singh J, Nagaraju J. A baculovirus-encoded MicroRNA (miRNA) suppresses its host miRNA biogenesis by regulating the exportin-5 cofactor Ran. J Virol 2012; 86:7867–7879 [View Article][PubMed]
     [Google Scholar]
  38. Zhang K, Chaillet JR, Perkins LA, Halazonetis TD, Perrimon N. Drosophila homolog of the mammalian jun oncogene is expressed during embryonic development and activates transcription in mammalian cells. Proc Natl Acad Sci USA 1990; 87:6281–6285 [View Article][PubMed]
     [Google Scholar]
  39. Ceballos-Olvera I, Chávez-Salinas S, Medina F, Ludert JE, del Angel RM. JNK phosphorylation, induced during dengue virus infection, is important for viral infection and requires the presence of cholesterol. Virology 2010; 396:30–36 [View Article][PubMed]
     [Google Scholar]
  40. Jang KL, Pulverer B, Woodgett JR, Latchman DS. Activation of the cellular transcription factor AP-1 in herpes simplex virus infected cells is dependent on the viral immediate-early protein ICPO. Nucleic Acids Res 1991; 19:4879–4883 [View Article][PubMed]
     [Google Scholar]
  41. McLean TI, Bachenheimer SL. Activation of cJUN N-terminal kinase by herpes simplex virus type 1 enhances viral replication. J Virol 1999; 73:8415–8426[PubMed]
     [Google Scholar]
  42. Xie J, Zhang S, Hu Y, Li D, Cui J et al. Regulatory roles of c-jun in H5N1 influenza virus replication and host inflammation. Biochim Biophys Acta 2014; 1842:2479–2488 [View Article][PubMed]
     [Google Scholar]
  43. Ludwig S, Ehrhardt C, Neumeier ER, Kracht M, Rapp UR et al. Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway. J Biol Chem 2001; 276:10990–10998 [View Article][PubMed]
     [Google Scholar]
  44. Kieser A, Kilger E, Gires O, Ueffing M, Kolch W et al. Epstein-Barr virus latent membrane protein-1 triggers AP-1 activity via the c-Jun N-terminal kinase cascade. EMBO J 1997; 16:6478–6485 [View Article][PubMed]
     [Google Scholar]
  45. Rahaus M, Wolff MH. Reciprocal effects of varicella-zoster virus (VZV) and AP1: activation of jun, fos and ATF-2 after VZV infection and their importance for the regulation of viral genes. Virus Res 2003; 92:9–21 [View Article][PubMed]
     [Google Scholar]
  46. Rajani KR, Pettit Kneller EL, Mckenzie MO, Horita DA, Chou JW et al. Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription. PLoS Pathog 2012; 8:e1002929 [View Article][PubMed]
     [Google Scholar]
  47. Yang CM, Lin CC, Lee IT, Lin YH, Yang CM et al. Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes. J Neuroinflammation 2012; 9:12 [View Article][PubMed]
     [Google Scholar]
  48. Twu JS, Lai MY, Chen DS, Robinson WS. Activation of protooncogene c-jun by the X protein of hepatitis B virus. Virology 1993; 192:346–350 [View Article][PubMed]
     [Google Scholar]
  49. Hutvágner G, Simard MJ, Mello CC, Zamore PD. Sequence-specific inhibition of small RNA function. PLoS Biol 2004; 2:e98 [View Article][PubMed]
     [Google Scholar]
  50. Leaman D, Chen PY, Fak J, Yalcin A, Pearce M et al. Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell 2005; 121:1097–1108 [View Article][PubMed]
     [Google Scholar]
  51. Reczko M, Maragkakis M, Alexiou P, Papadopoulos GL, Hatzigeorgiou AG. Accurate microRNA target prediction using detailed binding site accessibility and machine learning on proteomics data. Front Genet 2011; 2:103 [View Article][PubMed]
     [Google Scholar]
  52. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA 2004; 10:1507–1517 [View Article][PubMed]
     [Google Scholar]
  53. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4:44–57 [View Article][PubMed]
     [Google Scholar]
  54. Witkos TM, Koscianska E, Krzyzosiak WJ. Practical aspects of microRNA target prediction. Curr Mol Med 2011; 11:93–109 [View Article][PubMed]
     [Google Scholar]
  55. Kuhn DE, Martin MM, Feldman DS, Terry AV Jr, Nuovo GJ et al. Experimental validation of miRNA targets. Methods 2008; 44:47–54 [View Article][PubMed]
     [Google Scholar]
  56. Thomson DW, Bracken CP, Goodall GJ. Experimental strategies for microRNA target identification. Nucleic Acids Res 2011; 39:6845–6853 [View Article][PubMed]
     [Google Scholar]
  57. Hussain M, Asgari S. Functional analysis of a cellular microRNA in insect host-ascovirus interaction. J Virol 2010; 84:612–620 [View Article][PubMed]
     [Google Scholar]
  58. Perkins KK, Dailey GM, Tjian R. Novel Jun- and Fos-related proteins in Drosophila are functionally homologous to enhancer factor AP-1. Embo J 1988; 7:4265–4273[PubMed]
     [Google Scholar]
  59. Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene 2001; 20:2390–2400 [View Article][PubMed]
     [Google Scholar]
  60. Smeal T, Hibi M, Karin M. Altering the specificity of signal transduction cascades: positive regulation of c-Jun transcriptional activity by protein kinase A. Embo J 1994; 13:6006–6010[PubMed]
     [Google Scholar]
  61. Angel P, Allegretto EA, Okino ST, Hattori K, Boyle WJ et al. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature 1988; 332:166–171 [View Article][PubMed]
     [Google Scholar]
  62. Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK et al. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science 1987; 238:1386–1392 [View Article][PubMed]
     [Google Scholar]
  63. Angel P, Hattori K, Smeal T, Karin M. The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1. Cell 1988; 55:875–885 [View Article][PubMed]
     [Google Scholar]
  64. Wang GL, Goldstein ES. Transcription of Djun from D. melanogaster is positively regulated by DTF-1, AP-1, and CREB binding sites. Exp Cell Res 1994; 214:389–399 [View Article][PubMed]
     [Google Scholar]
  65. Merkling SH, Bronkhorst AW, Kramer JM, Overheul GJ, Schenck A et al. The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila. PLoS Pathog 2015; 11:e1004692 [View Article][PubMed]
     [Google Scholar]
  66. Li XF, Cao RB, Luo J, Fan JM, Wang JM et al. MicroRNA transcriptome profiling of mice brains infected with Japanese encephalitis virus by RNA sequencing. Infect Genet Evol 2016; 39:249–257 [View Article][PubMed]
     [Google Scholar]
  67. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006; 34:D140–D144 [View Article][PubMed]
     [Google Scholar]
  68. Lopez-Bergami P, Huang C, Goydos JS, Yip D, Bar-Eli M et al. Rewired ERK-JNK signaling pathways in melanoma. Cancer Cell 2007; 11:447–460 [View Article][PubMed]
     [Google Scholar]
  69. Majzoub K, Hafirassou ML, Meignin C, Goto A, Marzi S et al. RACK1 controls IRES-mediated translation of viruses. Cell 2014; 159:1086–1095 [View Article][PubMed]
     [Google Scholar]
  70. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4:E131E136 [View Article][PubMed]
     [Google Scholar]
  71. Best SM, Bloom ME. Caspase activation during virus infection: more than just the kiss of death?. Virology 2004; 320:191–194 [View Article][PubMed]
     [Google Scholar]
  72. Lim YM, Hayashi S, Tsuda L. Ebi/AP-1 suppresses pro-apoptotic genes expression and permits long-term survival of Drosophila sensory neurons. PLoS One 2012; 7:e37028 [View Article][PubMed]
     [Google Scholar]
  73. Katiyar S, Casimiro MC, Dettin L, Ju X, Wagner EF et al. C-jun inhibits mammary apoptosis in vivo. Mol Biol Cell 2010; 21:4264–4274 [View Article][PubMed]
     [Google Scholar]
  74. Ciapponi L, Bohmann D. An essential function of AP-1 heterodimers in Drosophila development. Mech Dev 2002; 115:35–40 [View Article][PubMed]
     [Google Scholar]
  75. Kockel L, Homsy JG, Bohmann D. Drosophila AP-1: lessons from an invertebrate. Oncogene 2001; 20:2347–2364 [View Article][PubMed]
     [Google Scholar]
  76. Hobert O. Gene regulation by transcription factors and microRNAs. Science 2008; 319:1785–1786 [View Article][PubMed]
     [Google Scholar]
  77. Xu Z, Bu Y, Chitnis N, Koumenis C, Fuchs SY et al. miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis. Nat Commun 2016; 7:11422 [View Article][PubMed]
     [Google Scholar]
  78. Osborne SE, Leong YS, O'Neill SL, Johnson KN. Variation in antiviral protection mediated by different Wolbachia strains in Drosophila simulans. PLoS Pathog 2009; 5:e1000656 [View Article][PubMed]
     [Google Scholar]
  79. Stevanovic AL, Arnold PA, Johnson KN. Wolbachia-mediated antiviral protection in Drosophila larvae and adults following oral infection. Appl Environ Microbiol 2015; 81:8215–8223 [View Article][PubMed]
     [Google Scholar]
  80. Hedges LM, Johnson KN. Induction of host defence responses by Drosophila C virus. J Gen Virol 2008; 89:1497–1501 [View Article][PubMed]
     [Google Scholar]
  81. Johnson KN, Christian PD. Molecular characterization of Drosophila C virus isolates. J Invertebr Pathol 1999; 73:248–254 [View Article][PubMed]
     [Google Scholar]
  82. Ekimler S, Sahin K. Computational methods for microRNA target prediction. Genes 2014; 5:671–683 [View Article][PubMed]
     [Google Scholar]
  83. Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L et al. Common features of microRNA target prediction tools. Front Genet 2014; 5:232014 [View Article][PubMed]
     [Google Scholar]
  84. Tarang S, Weston MD. Macros in microRNA target identification: a comparative analysis of in silico, in vitro, and in vivo approaches to microRNA target identification. RNA Biol 2014; 11:324–333 [View Article][PubMed]
     [Google Scholar]
  85. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37:1–13 [View Article][PubMed]
     [Google Scholar]
  86. Zhang G, Hussain M, O'Neill SL, Asgari S. Wolbachia uses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition in Aedes aegypti. Proc Natl Acad Sci USA 2013; 110:10276–10281 [View Article][PubMed]
     [Google Scholar]
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Drosophila microRNA modulates viral replication by targeting a homologue of mammalian cJun
J. Gen. Virol. 98, 1904 (2017); https://doi.org/10.1099/jgv.0.000831
/content/journal/jgv/10.1099/jgv.0.000831
/content/journal/jgv/10.1099/jgv.0.000831
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