1887

Abstract

MicroRNAs (miRNAs) are a class of short endogenous RNA molecules with the ability to control development, autophagy, apoptosis and the stress response in eukaryotes by pairing with partially complementary sites in the 3′ UTRs of targeted genes. Recent studies have demonstrated that miRNAs serve as critical effectors in intricate networks of host–pathogen interactions. Notably, we found that bta-miR-29b (referred to as miR-29b herein) was significantly upregulated >2.3-fold in bovine viral diarrhoea virus (BVDV) strain NADL-infected Madin–Darby bovine kidney (MDBK) cells 6 h post-infection compared with normal MDBK cells. However, the roles of miR-29b in BVDV infection and pathogenesis remain unclear. Here, we report the inhibitory effects of miR-29b on BVDV NADL replication and viral infection-related autophagy. miR-29b overexpression mediated by miRNA precursor-expressing lentivirus resulted in the attenuation of BVDV NADL infection-related autophagy by directly downregulating the intracellular expression levels of two key autophagy-associated proteins, ATG14 and ATG9A. Moreover, ATG14 and ATG9A overexpression rescue not only reversed miR-29b-inhibited autophagy, but also increased BVDV NADL replication. In previous studies, we found that the early stages of autophagy contributed to BVDV NADL replication in MDBK cells and that the inhibition of autophagy repressed BVDV NADL replication, which was also proved in the present study. Collectively, our results establish a novel link between miR-29b and viral replication, and also provide a new pathway for the intimate interaction between host cells and pathogens.

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2015-01-01
2019-10-19
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References

  1. Bandyopadhyay S., Friedman R. C., Marquez R. T., Keck K., Kong B., Icardi M. S., Brown K. E., Burge C. B., Schmidt W. N.. & other authors ( 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:, 1753–1762. [CrossRef][PubMed]
    [Google Scholar]
  2. Burman C., Ktistakis N. T.. ( 2010;). Autophagosome formation in mammalian cells. . Semin Immunopathol 32:, 397–413. [CrossRef][PubMed]
    [Google Scholar]
  3. Fang Z., Rajewsky N.. ( 2011;). The impact of miRNA target sites in coding sequences and in 3′ UTRs. . PLoS ONE 6:, e18067. [CrossRef][PubMed]
    [Google Scholar]
  4. Filipowicz W., Bhattacharyya S. N., Sonenberg N.. ( 2008;). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight. ? Nat Rev Genet 9:, 102–114. [CrossRef][PubMed]
    [Google Scholar]
  5. Foster J. L., Garcia J. V.. ( 2008;). HIV-1 Nef: at the crossroads. . Retrovirology 5:, 84. [CrossRef][PubMed]
    [Google Scholar]
  6. Frankel L. B., Wen J., Lees M., Høyer-Hansen M., Farkas T., Krogh A., Jäättelä M., Lund A. H.. ( 2011;). microRNA-101 is a potent inhibitor of autophagy. . EMBO J 30:, 4628–4641. [CrossRef][PubMed]
    [Google Scholar]
  7. Fu Q., Shi H., Zhang H., Ren Y., Guo F., Qiao J., Jia B., Wang P., Chen C.. ( 2013;). Autophagy during early stages contributes to bovine viral diarrhea virus replication in MDBK cells. . J Basic Microbiol doi:10.1002/jobm.201300750 [Epub ahead of print]. [CrossRef][PubMed]
    [Google Scholar]
  8. Ghosh Z., Mallick B., Chakrabarti J.. ( 2009;). Cellular versus viral microRNAs in host–virus interaction. . Nucleic Acids Res 37:, 1035–1048. [CrossRef][PubMed]
    [Google Scholar]
  9. He C., Klionsky D. J.. ( 2009;). Regulation mechanisms and signaling pathways of autophagy. . Annu Rev Genet 43:, 67–93. [CrossRef][PubMed]
    [Google Scholar]
  10. Iorio M. V., Ferracin M., Liu C. G., Veronese A., Spizzo R., Sabbioni S., Magri E., Pedriali M., Fabbri M.. & other authors ( 2005;). MicroRNA gene expression deregulation in human breast cancer. . Cancer Res 65:, 7065–7070. [CrossRef][PubMed]
    [Google Scholar]
  11. Itakura E., Kishi-Itakura C., Koyama-Honda I., Mizushima N.. ( 2012;). Structures containing Atg9A and the ULK1 complex independently target depolarized mitochondria at initial stages of Parkin-mediated mitophagy. . J Cell Sci 125:, 1488–1499. [CrossRef][PubMed]
    [Google Scholar]
  12. Jopling C. L., 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:, 77–85. [CrossRef][PubMed]
    [Google Scholar]
  13. Kihara A., Noda T., Ishihara N., Ohsumi Y.. ( 2001;). Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. . J Cell Biol 152:, 519–530. [CrossRef][PubMed]
    [Google Scholar]
  14. Klionsky D. J., Abdalla F. C., Abeliovich H., Abraham R. T., Acevedo-Arozena A., Adeli K., Agholme L., Agnello M., Agostinis P.. & other authors ( 2012;). Guidelines for the use and interpretation of assays for monitoring autophagy. . Autophagy 8:, 445–544. [CrossRef][PubMed]
    [Google Scholar]
  15. Kloosterman W. P., Plasterk R. H.. ( 2006;). The diverse functions of microRNAs in animal development and disease. . Dev Cell 11:, 441–450. [CrossRef][PubMed]
    [Google Scholar]
  16. Korkmaz G., le Sage C., Tekirdag K. A., Agami R., Gozuacik D.. ( 2012;). miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. . Autophagy 8:, 165–176. [CrossRef][PubMed]
    [Google Scholar]
  17. Kyei G. B., Dinkins C., Davis A. S., Roberts E., Singh S. B., Dong C., Wu L., Kominami E., Ueno T.. & other authors ( 2009;). Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. . J Cell Biol 186:, 255–268. [CrossRef][PubMed]
    [Google Scholar]
  18. Lackner T., Müller A., Pankraz A., Becher P., Thiel H. J., Gorbalenya A. E., Tautz N.. ( 2004;). Temporal modulation of an autoprotease is crucial for replication and pathogenicity of an RNA virus. . J Virol 78:, 10765–10775. [CrossRef][PubMed]
    [Google Scholar]
  19. Levine B., Kroemer G.. ( 2008;). Autophagy in the pathogenesis of disease. . Cell 132:, 27–42. [CrossRef][PubMed]
    [Google Scholar]
  20. Liang X. H., Kleeman L. K., Jiang H. H., Gordon G., Goldman J. E., Berry G., Herman B., Levine B.. ( 1998;). Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. . J Virol 72:, 8586–8596.[PubMed]
    [Google Scholar]
  21. Livak K. J., Schmittgen T. D.. ( 2001;). Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. . Methods 25:, 402–408. [CrossRef][PubMed]
    [Google Scholar]
  22. Mehrpour M., Esclatine A., Beau I., Codogno P.. ( 2010;). Overview of macroautophagy regulation in mammalian cells. . Cell Res 20:, 748–762. [CrossRef][PubMed]
    [Google Scholar]
  23. Mizushima N.. ( 2004;). Methods for monitoring autophagy. . Int J Biochem Cell Biol 36:, 2491–2502. [CrossRef][PubMed]
    [Google Scholar]
  24. Obara K., Ohsumi Y.. ( 2011;). Atg14: a key player in orchestrating autophagy. . Int J Cell Biol 2011:, 713435. [CrossRef][PubMed]
    [Google Scholar]
  25. Obara K., Sekito T., Ohsumi Y.. ( 2006;). Assortment of phosphatidylinositol 3-kinase complexes–Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. . Mol Biol Cell 17:, 1527–1539. [CrossRef][PubMed]
    [Google Scholar]
  26. Olivieri K. C., Mukerji J., Gabuzda D.. ( 2011;). Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2. . Retrovirology 8:, 64. [CrossRef][PubMed]
    [Google Scholar]
  27. Otsuka M., Jing Q., Georgel P., New L., Chen J., Mols J., Kang Y. J., Jiang Z., Du X.. & other authors ( 2007;). Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. . Immunity 27:, 123–134. [CrossRef][PubMed]
    [Google Scholar]
  28. Perdrizet J. A., Rebhun W. C., Dubovi E. J., Donis R. O.. ( 1987;). Bovine virus diarrhea – clinical syndromes in dairy herds. . Cornell Vet 77:, 46–74.[PubMed]
    [Google Scholar]
  29. Qin W., Chung A. C., Huang X. R., Meng X. M., Hui D. S., Yu C. M., Sung J. J., Lan H. Y.. ( 2011;). TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. . J Am Soc Nephrol 22:, 1462–1474. [CrossRef][PubMed]
    [Google Scholar]
  30. Reed L. J., Muench H.. ( 1938;). A simple method of estimating fifty per cent endpoints. . Am J Epidemiol 27:, 493–497.
    [Google Scholar]
  31. Roderburg C., Urban G. W., Bettermann K., Vucur M., Zimmermann H., Schmidt S., Janssen J., Koppe C., Knolle P.. & other authors ( 2011;). Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. . Hepatology 53:, 209–218. [CrossRef][PubMed]
    [Google Scholar]
  32. Svensson L., Hjalmarsson A., Everitt E.. ( 1999;). TCID50 determination by an immuno dot blot assay as exemplified in a study of storage conditions of infectious pancreatic necrosis virus. . J Virol Methods 80:, 17–24. [CrossRef][PubMed]
    [Google Scholar]
  33. Tamura H., Shibata M., Koike M., Sasaki M., Uchiyama Y.. ( 2010;). Atg9A protein, an autophagy-related membrane protein, is localized in the neurons of mouse brains. . J Histochem Cytochem 58:, 443–453. [CrossRef][PubMed]
    [Google Scholar]
  34. Tang J.-Y., Hsi E., Huang Y.-C., Hsu N. C.-H., Chen Y.-K., Chu P.-Y., Chai C.-Y.. ( 2013;). ATG9A overexpression is associated with disease recurrence and poor survival in patients with oral squamous cell carcinoma. . Virchows Arch 463:, 737–742. [CrossRef][PubMed]
    [Google Scholar]
  35. Tiscornia G., Singer O., Verma I. M.. ( 2006;). Production and purification of lentiviral vectors. . Nat Protoc 1:, 241–245. [CrossRef][PubMed]
    [Google Scholar]
  36. Tsunetsugu-Yokota Y., Yamamoto T.. ( 2010;). Mammalian microRNAs: post-transcriptional gene regulation in RNA virus infection and therapeutic applications. . Front Microbiol 1:, 108. [CrossRef][PubMed]
    [Google Scholar]
  37. van Rooij E., Sutherland L. B., Thatcher J. E., DiMaio J. M., Naseem R. H., Marshall W. S., Hill J. A., Olson E. N.. ( 2008;). Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. . Proc Natl Acad Sci U S A 105:, 13027–13032. [CrossRef][PubMed]
    [Google Scholar]
  38. Wang C. M., Wang Y., Fan C. G., Xu F. F., Sun W. S., Liu Y. G., Jia J. H.. ( 2011;). miR-29c targets TNFAIP3, inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. . Biochem Biophys Res Commun 411:, 586–592. [CrossRef][PubMed]
    [Google Scholar]
  39. Yao T. P.. ( 2010;). The role of ubiquitin in autophagy-dependent protein aggregate processing. . Genes Cancer 1:, 779–786. [CrossRef][PubMed]
    [Google Scholar]
  40. Yu Y., Cao L., Yang L., Kang R., Lotze M., Tang D.. ( 2012;). microRNA 30A promotes autophagy in response to cancer therapy. . Autophagy 8:, 853–855. [CrossRef][PubMed]
    [Google Scholar]
  41. Zheng Z., Ke X., Wang M., He S., Li Q., Zheng C., Zhang Z., Liu Y., Wang H.. ( 2013;). Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome. . J Virol 87:, 5645–5656. [CrossRef][PubMed]
    [Google Scholar]
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