Vaccinia virus infection suppresses the cell microRNA machinery (original) (raw)

Abstract

MicroRNAs are key players in the regulation of gene expression by posttranscriptional suppression. They are involved in physiological processes, and thus their deregulation may contribute to the development of diseases and progression of cancer. Virus-encoded microRNAs and microRNAs of host origin play an important role in controlling the virus life cycle and immunity. The aim of this study was to determine the effect of vaccinia virus (VACV) infection on the expression of host-encoded microRNAs. A marked general suppression of most microRNAs in the infected cells was observed within 24 hours after VACV infection of a number of cell types. We demonstrate that this suppression was associated with abrogation of expression of the Dicer1 enzyme, which is a key enzyme in the generation of microRNAs.

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References

  1. Moss B (1996) Poxviridae: the viruses and their replication. In: Fields BN, Knipe DM, Howley PM (eds) Fields virology, vol 3. Lippincott-Raven, New York, p 2637
    Google Scholar
  2. Katsafanas GC, Moss B (2007) Colocalization of transcription and translation within cytoplasmic poxvirus factories coordinates viral expression and subjugates host functions. Cell Host Microbe. doi:10.1016/j.chom.2007.08.005
    PubMed Google Scholar
  3. Schramm B, Locker JK (2005) Cytoplasmic organization of POXvirus DNA replication. Traffic. doi:10.1111/j.1600-0854.2005.00324.x
    Google Scholar
  4. Parrish S, Resch W, Moss B (2007) Vaccinia virus D10 protein has mRNA decapping activity, providing a mechanism for control of host and viral gene expression. Proc Natl Acad Sci USA. doi:10.1073/pnas.0611685104
    Google Scholar
  5. Parrish S, Moss B (2007) Characterization of a second vaccinia virus mRNA-decapping enzyme conserved in poxviruses. J Virol. doi:10.1128/JVI.01668-07
    Google Scholar
  6. Boone RF, Parr RP, Moss B (1979) Intermolecular duplexes formed from polyadenylylated vaccinia virus RNA. J Virol 30:365–374
    PubMed CAS Google Scholar
  7. Arsenio J, Deschambault Y, Cao J (2008) Antagonizing activity of vaccinia virus E3L against human interferons in Huh7 cells. Virology. doi:10.1016/j.virol.2008.04.014
    PubMed Google Scholar
  8. Carroll K, Elroy-Stein O, Moss B, Jagus R (1993) Recombinant vaccinia virus K3L gene product prevents activation of double-stranded RNA-dependent, initiation factor 2 alpha-specific protein kinase. J Biol Chem 268:12837–12842
    PubMed CAS Google Scholar
  9. Chang HW, Watson JC, Jacobs BL (1992) The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci USA 89:4825–4829
    Article PubMed CAS Google Scholar
  10. Haga IR, Bowie AG (2005) Evasion of innate immunity by vaccinia virus. Parasitology. doi:10.1017/S0031182005008127
    PubMed Google Scholar
  11. Rivas C, Gil J, Melkova Z, Esteban M, Diaz-Guerra M (1998) Vaccinia virus E3L protein is an inhibitor of the interferon (i.f.n.)-induced 2–5A synthetase enzyme. Virology 248:406–414
    Article Google Scholar
  12. Wang J, Xu R, Lin F, Zhang S, Zhang G, Hu S, Zheng Z (2008) MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart. Cardiology. doi:10.1159/000172616
    Google Scholar
  13. Schickel R, Boyerinas B, Park SM, Peter ME (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. doi:10.1038/onc.2008.274
    PubMed Google Scholar
  14. 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. doi:10.1128/JVI.02575-07
    Google Scholar
  15. Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. doi:10.1038/nrm1644
    Google Scholar
  16. Carthew RW, Sontheimer EJ (2009) Origins and Mechanisms of miRNAs and siRNAs. Cell. doi:10.1016/j.cell.2009.01.035
    Google Scholar
  17. Hammond SM, Bernstein E, Beach D, Hannon GJ (2000) An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. doi:10.1038/35005107
    Google Scholar
  18. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
    Article PubMed CAS Google Scholar
  19. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR (2005) Kaposi’s sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci USA. doi:10.1073/pnas.0408192102
    Google Scholar
  20. Cai X, Schafer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, Raab-Traub N, Cullen BR (2006) Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. doi:10.1371/journal.ppat.0020023
    Google Scholar
  21. Grey F, Nelson J (2008) Identification and function of human cytomegalovirus microRNAs. J Clin Virol. doi:10.1016/j.jcv.2007.11.024
    PubMed Google Scholar
  22. 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. doi:10.1126/science.1096781
    PubMed Google Scholar
  23. Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR (2009) Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J Virol. doi:10.1128/JVI.01185-09
    Google Scholar
  24. Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K, Cardinaud B, Maurin T, Barbry P, Baillat V, Reynes J, Corbeau P, Jeang KT, Benkirane M (2007) Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. doi:10.1126/science.1136319
    PubMed Google Scholar
  25. Aliyari R, Ding SW (2009) RNA-based viral immunity initiated by the Dicer family of host immune receptors. Immunol Rev. doi:10.1111/j.1600-065X.2008.00722.x
    PubMed Google Scholar
  26. Obbard DJ, Gordon KH, Buck AH, Jiggins FM (2009) The evolution of RNAi as a defence against viruses and transposable elements. Philos Trans R Soc Lond B Biol Sci. doi:10.1098/rstb.2008.0168
    PubMed Google Scholar
  27. van Rij RP, Berezikov E (2009) Small RNAs and the control of transposons and viruses in Drosophila. Trends Microbiol. doi:10.1016/j.tim.2009.01.003
    PubMed Google Scholar
  28. Otsuka M, Jing Q, Georgel P, New L, Chen J, Mols J, Kang YJ, Jiang Z, Du X, Cook R, Das SC, Pattnaik AK, Beutler B, Han J (2007) Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity. doi:10.1016/j.immuni.2007.05.014
    PubMed Google Scholar
  29. Ronen R, Gan I, Modai S, Sukacheov A, Dror G, Halperin E, Shomron N (2010) miRNAkey: a software for microRNA deep sequencing analysis. Bioinformatics. doi:10.1093/bioinformatics/btq493
    PubMed Google Scholar
  30. Lu S, Cullen BR (2004) Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and MicroRNA biogenesis. J Virol. doi:10.1128/JVI.78.23.12868-12876.2004
    Google Scholar
  31. Andersson MG, Haasnoot PC, Xu N, Berenjian S, Berkhout B, Akusjarvi G (2005) Suppression of RNA interference by adenovirus virus-associated RNA. J Virol. doi:10.1128/JVI.79.15.9556-9565.2005
    Google Scholar
  32. Muller S, Imler JL (2007) Dicing with viruses: microRNAs as antiviral factors. Immunity. doi:10.1016/j.immuni.2007.07.003
    Google Scholar
  33. Hikichi M, Kidokoro M, Haraguchi T, Iba H, Shida H, Tahara H, Nakamura T (2011) MicroRNA regulation of glycoprotein B5R in oncolytic vaccinia virus reduces viral pathogenicity without impairing its antitumor efficacy. Mol Ther. doi:10.1038/mt.2011.36
    PubMed Google Scholar

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Acknowledgment

This work was supported by the Israel Science Foundation (grant no. 1375/05) and the Israel Ministry for Science, Culture, and Sport (grant no. 3-4435). The sponsor had no role in the study.

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Authors and Affiliations

  1. Department of Virology and Molecular Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, 84105, Beer Sheva, Israel
    Moran Grinberg, Zvi Bentwich & Yonat Shemer-Avni
  2. Rosetta Genomics Ltd., 10 Plaut St., 76706, Rehovot, Israel
    Shlomit Gilad, Eti Meiri & Asaf Levy
  3. Cell and Developmental Biology, Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel
    Ofer Isakov, Roy Ronen & Noam Shomron

Authors

  1. Moran Grinberg
  2. Shlomit Gilad
  3. Eti Meiri
  4. Asaf Levy
  5. Ofer Isakov
  6. Roy Ronen
  7. Noam Shomron
  8. Zvi Bentwich
  9. Yonat Shemer-Avni

Corresponding author

Correspondence toYonat Shemer-Avni.

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705_2012_1366_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 55 kb)Supplemental Figure 1 Abrogation of Dicer1 in a variety of VACV-infected cells. HeLa, Vero and 293 cells were infected with VACV for 48 h (white bars) or mock-infected (black bars). Following infection, total RNA was extracted, and SYBR green RT-PCR was performed to measure transcription of Drosha (panel a) and Dicer1 (panel b) mRNAs. While Dicer1 expression was abolished in infected cells (panel b), there was no difference in Drosha expression in infected vs. uninfected cells (panel a). The average of the data from two experiments is shown

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Grinberg, M., Gilad, S., Meiri, E. et al. Vaccinia virus infection suppresses the cell microRNA machinery.Arch Virol 157, 1719–1727 (2012). https://doi.org/10.1007/s00705-012-1366-z

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