1887

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Volume 97, Issue 1

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity Free

Abstract

In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 3′ untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 3′ UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 3′ UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.

  • Received:
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© 2015 The Authors
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2016-01-01
2024-04-19
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References

  1. Allen R. M., Marquart T. J., Albert C. J., Suchy F. J., Wang D. Q., Ananthanarayanan M., Ford D. A., Baldán A. 2012; miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity. EMBO Mol Med 4:882–895 [View Article][PubMed]
     [Google Scholar]
  2. Andersson M. G., Haasnoot P. C., Xu N., Berenjian S., Berkhout B., Akusjärvi G. 2005; Suppression of RNA interference by adenovirus virus-associated RNA. J Virol 79:9556–9565 [View Article][PubMed]
     [Google Scholar]
  3. Betel D., Wilson M., Gabow A., Marks D. S., Sander C. 2008; The microRNA.org resource: targets and expression. Nucleic Acids Res 36:D149–D153 [View Article][PubMed]
     [Google Scholar]
  4. Brass A. L., Huang I. C., Benita Y., John S. P., Krishnan M. N., Feeley E. M., Ryan B. J., Weyer J. L., van der Weyden L., other authors. 2009; The IFITM proteins mediate cellular resistance to influenza A H1N1 virus. West Nile virus, and dengue virus. Cell 139:1243–1254 [View Article][PubMed]
     [Google Scholar]
  5. Buggele W. A., Krause K. E., Horvath C. M. 2013; Small RNA profiling of influenza A virus-infected cells identifies miR-449b as a regulator of histone deacetylase 1 and interferon beta. PLoS One 8:e76560 [View Article][PubMed]
     [Google Scholar]
  6. Cirera-Salinas D., Pauta M., Allen R. M., Salerno A. G., Ramírez C. M., Chamorro-Jorganes A., Wanschel A. C., Lasuncion M. A., Morales-Ruiz M., other authors. 2012; miR-33 regulates cell proliferation and cell cycle progression. Cell Cycle 11:922–933 [View Article][PubMed]
     [Google Scholar]
  7. De Tullio G., De Fazio V., Sgherza N., Minoia C., Serratì S., Merchionne F., Loseto G., Iacobazzi A., Rana A., other authors. 2014; Challenges and opportunities of microRNAs in lymphomas. Molecules 19:14723–14781 [View Article][PubMed]
     [Google Scholar]
  8. Desai T. M., Marin M., Chin C. R., Savidis G., Brass A. L., Melikyan G. B. 2014; IFITM3 restricts influenza A virus entry by blocking the formation of fusion pores following virus–endosome hemifusion. PLoS Pathog 10:e1004048 [View Article][PubMed]
     [Google Scholar]
  9. Eisfeld A. J., Neumann G., Kawaoka Y. 2015; At the centre: influenza A virus ribonucleoproteins. Nat Rev Microbiol 13:28–41 [View Article][PubMed]
     [Google Scholar]
  10. Everitt A. R., Clare S., Pertel T., John S. P., Wash R. S., Smith S. E., Chin C. R., Feeley E. M., Sims J. S., other authors. 2012; IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484:519–523 [View Article][PubMed]
     [Google Scholar]
  11. Han Q., Chang C., Li L., Klenk C., Cheng J., Chen Y., Xia N., Shu Y., Chen Z., other authors. 2014; Sumoylation of influenza A virus nucleoprotein is essential for intracellular trafficking and virus growth. J Virol 88:9379–9390 [View Article][PubMed]
     [Google Scholar]
  12. Hao L., Sakurai A., Watanabe T., Sorensen E., Nidom C. A., Newton M. A., Ahlquist P., Kawaoka Y. 2008; Drosophila RNAi screen identifies host genes important for influenza virus replication. Nature 454:890–893 [View Article][PubMed]
     [Google Scholar]
  13. He Y., Xu K., Keiner B., Zhou J., Czudai V., Li T., Chen Z., Liu J., Klenk H. D., other authors. 2010; Influenza A virus replication induces cell cycle arrest in G0/G1 phase. J Virol 84:12832–12840 [View Article][PubMed]
     [Google Scholar]
  14. Hudjetz B., Gabriel G. 2012; Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7. PLoS Pathog 8:e1002488 [View Article][PubMed]
     [Google Scholar]
  15. Izzard L., Ye S., Jenkins K., Xia Y., Tizard M., Stambas J. 2014; miRNA modulation of SOCS1 using an influenza A virus delivery system. J Gen Virol 95:1880–1885 [View Article][PubMed]
     [Google Scholar]
  16. Karlas A., Machuy N., Shin Y., Pleissner K. P., Artarini A., Heuer D., Becker D., Khalil H., Ogilvie L. A., other authors. 2010; Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication. Nature 463:818–822 [View Article][PubMed]
     [Google Scholar]
  17. König R., Stertz S., Zhou Y., Inoue A., Hoffmann H. H., Bhattacharyya S., Alamares J. G., Tscherne D. M., Ortigoza M. B., other authors. 2010; Human host factors required for influenza virus replication. Nature 463:813–817 [View Article][PubMed]
     [Google Scholar]
  18. Li Y., Chan E. Y., Li J., Ni C., Peng X., Rosenzweig E., Tumpey T. M., Katze M. G. 2010; MicroRNA expression and virulence in pandemic influenza virus-infected mice. J Virol 84:3023–3032 [View Article][PubMed]
     [Google Scholar]
  19. Liu X., Sun L., Yu M., Wang Z., Xu C., Xue Q., Zhang K., Ye X., Kitamura Y., Liu W. 2009; Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication. Cell Microbiol 11:730–741 [View Article][PubMed]
     [Google Scholar]
  20. Loveday E. K., Svinti V., Diederich S., Pasick J., Jean F. 2012; Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection. J Virol 86:6109–6122 [View Article][PubMed]
     [Google Scholar]
  21. Lu S., Cullen B. R. 2004; Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis. J Virol 78:12868–12876 [View Article][PubMed]
     [Google Scholar]
  22. Ma Y. J., Yang J., Fan X. L., Zhao H. B., Hu W., Li Z. P., Yu G. C., Ding X. R., Wang J. Z., other authors. 2012; Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells. J Cell Mol Med 16:2539–2546 [View Article][PubMed]
     [Google Scholar]
  23. Marcinowski L., Tanguy M., Krmpotic A., Rädle B., Lisnić V. J., Tuddenham L., Chane-Woon-Ming B., Ruzsics Z., Erhard F., other authors. 2012; Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo. PLoS Pathog 8:e1002510 [View Article][PubMed]
     [Google Scholar]
  24. Neumann G., Watanabe T., Ito H., Watanabe S., Goto H., Gao P., Hughes M., Perez D. R., Donis R., other authors. 1999; Generation of influenza A viruses entirely from cloned cDNAs. Proc Natl Acad Sci U S A 96:9345–9350 [View Article][PubMed]
     [Google Scholar]
  25. Noda T., Kawaoka Y. 2012; Packaging of influenza virus genome: robustness of selection. Proc Natl Acad Sci U S A 109:8797–8798 [View Article][PubMed]
     [Google Scholar]
  26. Pinto L. H., Holsinger L. J., Lamb R. A. 1992; Influenza virus M2 protein has ion channel activity. Cell 69:517–528 [View Article][PubMed]
     [Google Scholar]
  27. Rosenberger C. M., Podyminogin R. L., Navarro G., Zhao G. W., Askovich P. S., Weiss M. J., Aderem A. 2012; miR-451 regulates dendritic cell cytokine responses to influenza infection. J Immunol 189:5965–5975 [View Article][PubMed]
     [Google Scholar]
  28. Ruike Y., Ichimura A., Tsuchiya S., Shimizu K., Kunimoto R., Okuno Y., Tsujimoto G. 2008; Global correlation analysis for micro-RNA and mRNA expression profiles in human cell lines. J Hum Genet 53:515–523 [View Article][PubMed]
     [Google Scholar]
  29. Song L., Liu H., Gao S., Jiang W., Huang W. 2010; Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol 84:8849–8860 [View Article][PubMed]
     [Google Scholar]
  30. Stauffer S., Feng Y., Nebioglu F., Heilig R., Picotti P., Helenius A. 2014; Stepwise priming by acidic pH and a high K+ concentration is required for efficient uncoating of influenza A virus cores after penetration. J Virol 88:13029–13046 [View Article][PubMed]
     [Google Scholar]
  31. Sun E., He J., Zhuang X. 2013; Dissecting the role of COPI complexes in influenza virus infection. J Virol 87:2673–2685 [View Article][PubMed]
     [Google Scholar]
  32. Thomas M., Lange-Grünweller K., Weirauch U., Gutsch D., Aigner A., Grünweller A., Hartmann R. K. 2012; The proto-oncogene Pim-1 is a target of miR-33a. Oncogene 31:918–928 [View Article][PubMed]
     [Google Scholar]
  33. Wang J. M., Zhou J. J., Zheng Q., Gan H., Wang H. 2014; Dialysis method alters the expression of microRNA-33a and its target genes ABCA1, ABCG1 in THP-1 macrophages. Ther Apher Dial 18:44–50 [View Article][PubMed]
     [Google Scholar]
  34. Wijesekara N., Zhang L. H., Kang M. H., Abraham T., Bhattacharjee A., Warnock G. L., Verchere C. B., Hayden M. R. 2012; miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets. Diabetes 61:653–658 [View Article][PubMed]
     [Google Scholar]
  35. Zhang J., Li G., Ye X. 2010; Cyclin T1/CDK9 interacts with influenza A virus polymerase and facilitates its association with cellular RNA polymerase II. J Virol 84:12619–12627 [View Article][PubMed]
     [Google Scholar]
  36. Zhang X., Dong C., Sun X., Li Z., Zhang M., Guan Z., Duan M. 2014; Induction of the cellular miR-29c by influenza virus inhibits the innate immune response through protection of A20 mRNA. Biochem Biophys Res Commun 450:755–761 [View Article][PubMed]
     [Google Scholar]
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MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity
J. Gen. Virol. 97, 27 (2016); https://doi.org/10.1099/jgv.0.000311
/content/journal/jgv/10.1099/jgv.0.000311
/content/journal/jgv/10.1099/jgv.0.000311
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