1887

Journal of General Virology header logo

Volume 98, Issue 4

Cellular microRNA miR-10a-5p inhibits replication of porcine reproductive and respiratory syndrome virus by targeting the host factor signal recognition particle 14 Free

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important viruses affecting the swine industry worldwide. MicroRNAs have recently been demonstrated to play vital roles in virus–host interactions. Our previous research on small RNA deep sequencing showed that the expression level of miR-10a increased during the viral life cycle. The present study sought to determine the function of miR-10a and its molecular mechanism during PRRSV infection. In the current study, the result of PRRSV infection inducing miR-10a expression was validated by quantitative reverse transcriptase PCR. Overexpression of miR-10a-5p using its mimics markedly reduced the expression level of intracellular PRRSV ORF7 mRNA and N protein. Simultaneously, overexpression of miR-10a-5p also significantly decreased the expression level of extracellular viral RNA and virus titres in the supernatants. These results demonstrated that miR-10a-5p could suppress the replication of PRRSV. A direct interaction between miR-10a-5p and signal recognition particle 14 (SRP14) was confirmed using bioinformatic prediction and experimental verification. miR-10a-5p could directly target the 3′UTR of pig SRP14 mRNA in a sequence-specific manner and decrease SRP14 expression through translational repression but not mRNA degradation. Further, knockdown of SRP14 by small interfering RNA also inhibits the replication of PRRSV. Collectively, these results suggested that miR-10a-5p inhibits PRRSV replication through suppression of SRP14 expression, which not only provides new insights into virus–host interactions during PRRSV infection but also suggests potential new antiviral strategies against PRRSV infection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): miRNA , post-transcriptional regulation , PRRSV , SRP14 and virus–cell interaction
© 2017 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000708
2017-04-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/4/624.html?itemId=/content/journal/jgv/10.1099/jgv.0.000708&mimeType=html&fmt=ahah

References

  1. Snijder EJ, Kikkert M, Fang Y. Arterivirus molecular biology and pathogenesis. J Gen Virol 2013; 94:2141–2163 [View Article][PubMed]
     [Google Scholar]
  2. Brar MS, Shi M, Hui RK, Leung FC. Genomic evolution of porcine reproductive and respiratory syndrome virus (PRRSV) isolates revealed by deep sequencing. PLoS One 2014; 9:e88807 [View Article][PubMed]
     [Google Scholar]
  3. Rappe JC, García-Nicolás O, Flückiger F, Thür B, Hofmann MA et al. Heterogeneous antigenic properties of the porcine reproductive and respiratory syndrome virus nucleocapsid. Vet Res 2016; 47:117 [View Article][PubMed]
     [Google Scholar]
  4. Wells KD, Bardot R, Whitworth KM, Trible BR, Fang Y et al. Replacement of porcine CD163 scavenger receptor cysteine-rich domain 5 with a CD163-Like homolog confers resistance of pigs to genotype 1 but not genotype 2 porcine reproductive and respiratory syndrome virus. J Virol 2017; 91:e01521-16 [View Article][PubMed]
     [Google Scholar]
  5. Lu Q, Bai J, Zhang L, Liu J, Jiang Z et al. Two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling approach revealed first proteome profiles of pulmonary alveolar macrophages infected with porcine reproductive and respiratory syndrome virus. J Proteome Res 2012; 11:2890–2903 [View Article][PubMed]
     [Google Scholar]
  6. Bao D, Wang R, Qiao S, Wan B, Wang Y et al. Antibody-dependent enhancement of PRRSV infection down-modulates TNF-α and IFN-β transcription in macrophages. Vet Immunol Immunopathol 2013; 156:128–134 [View Article]
     [Google Scholar]
  7. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136:215–233 [View Article][PubMed]
     [Google Scholar]
  8. Gottwein E, Cullen BR. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe 2008; 3:375–387 [View Article][PubMed]
     [Google Scholar]
  9. Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annu Rev Microbiol 2010; 64:123–141 [View Article][PubMed]
     [Google Scholar]
  10. Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science 2005; 309:1577–1581 [View Article][PubMed]
     [Google Scholar]
  11. Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M et al. miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat Cell Biol 2010; 12:513–519 [View Article]
     [Google Scholar]
  12. Cong P, Xiao S, Chen Y, Wang L, Gao J et al. Integrated miRNA and mRNA transcriptomes of porcine alveolar macrophages (PAM cells) identifies strain-specific miRNA molecular signatures associated with H-PRRSV and N-PRRSV infection. Mol Biol Rep 2014; 41:5863–5875 [View Article]
     [Google Scholar]
  13. Kincaid RP, Sullivan CS. Virus-encoded microRNAs: an overview and a look to the future. PLoS Pathog 2012; 8:e1003018 [View Article][PubMed]
     [Google Scholar]
  14. O'Connor CM, Vanicek J, Murphy EA. Host microRNA regulation of human cytomegalovirus immediate early protein translation promotes viral latency. J Virol 2014; 88:5524–5532 [View Article][PubMed]
     [Google Scholar]
  15. Masaki T, Arend KC, Li Y, Yamane D, McGivern DR et al. miR-122 stimulates hepatitis C virus RNA synthesis by altering the balance of viral RNAs engaged in replication versus translation. Cell Host Microbe 2015; 17:217–228 [View Article][PubMed]
     [Google Scholar]
  16. Jangra RK, Yi M, Lemon SM. Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. J Virol 2010; 84:6615–6625 [View Article][PubMed]
     [Google Scholar]
  17. Perez JT, Varble A, Sachidanandam R, Zlatev I, Manoharan M et al. Influenza A virus-generated small RNAs regulate the switch from transcription to replication. Proc Natl Acad Sci USA 2010; 107:11525–11530 [View Article]
     [Google Scholar]
  18. Hussain M, Torres S, Schnettler E, Funk A, Grundhoff A et al. West Nile virus encodes a microRNA-like small RNA in the 3′ untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells. Nucleic Acids Res 2012; 40:2210–2223 [View Article][PubMed]
     [Google Scholar]
  19. Hussain M, Asgari S. MicroRNA-like viral small RNA from dengue virus 2 autoregulates its replication in mosquito cells. Proc Natl Acad Sci USA 2014; 111:2746–2751 [View Article]
     [Google Scholar]
  20. Gao L, Guo XK, Wang L, Zhang Q, Li N et al. MicroRNA 181 suppresses porcine reproductive and respiratory syndrome virus (PRRSV) infection by targeting PRRSV receptor CD163. J Virol 2013; 87:8808–8812 [View Article][PubMed]
     [Google Scholar]
  21. Guo XK, Zhang Q, Gao L, Li N, Chen XX et al. Increasing expression of microRNA 181 inhibits porcine reproductive and respiratory syndrome virus replication and has implications for controlling virus infection. J Virol 2013; 87:1159–1171 [View Article][PubMed]
     [Google Scholar]
  22. Li L, Wei Z, Zhou Y, Gao F, Jiang Y et al. Host miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by upregulating type I interferons. Virus Res 2015; 195:86–94 [View Article]
     [Google Scholar]
  23. Jia X, Bi Y, Li J, Xie Q, Yang H et al. Cellular microRNA miR-26a suppresses replication of porcine reproductive and respiratory syndrome virus by activating innate antiviral immunity. Sci Rep 2015; 5:10651 [View Article][PubMed]
     [Google Scholar]
  24. Zhang Q, Huang C, Yang Q, Gao L, Liu HC et al. MicroRNA-30c modulates type I IFN responses to facilitate porcine reproductive and respiratory syndrome virus infection by targeting JAK1. J Immunol 2016; 196:2272–2282 [View Article][PubMed]
     [Google Scholar]
  25. Wang D, Cao L, Xu Z, Fang L, Zhong Y et al. MiR-125b reduces porcine reproductive and respiratory syndrome virus replication by negatively regulating the NF-κB pathway. PLoS One 2013; 8:e55838 [View Article][PubMed]
     [Google Scholar]
  26. Li N, Yan Y, Zhang A, Gao J, Zhang C et al. MicroRNA-like viral small RNA from porcine reproductive and respiratory syndrome virus negatively regulates viral replication by targeting the viral nonstructural protein 2. Oncotarget 2016; 7:82902–82920 [View Article][PubMed]
     [Google Scholar]
  27. Xiao S, Wang X, Ni H, Li N, Zhang A et al. MicroRNA miR-24-3p promotes porcine reproductive and respiratory syndrome virus replication through suppression of heme oxygenase-1 expression. J Virol 2015; 89:4494–4503 [View Article][PubMed]
     [Google Scholar]
  28. Xiao S, Du T, Wang X, Ni H, Yan Y et al. MiR-22 promotes porcine reproductive and respiratory syndrome virus replication by targeting the host factor HO-1. Vet Microbiol 2016; 192:226–230 [View Article]
     [Google Scholar]
  29. Lund AH. miR-10 in development and cancer. Cell Death Differ 2010; 17:209–214 [View Article]
     [Google Scholar]
  30. Havelange V, Ranganathan P, Geyer S, Nicolet D, Huang X et al. Implications of the miR-10 family in chemotherapy response of NPM1-mutated AML. Blood 2014; 123:2412–2415 [View Article]
     [Google Scholar]
  31. Varnholt H, Drebber U, Schulze F, Wedemeyer I, Schirmacher P et al. MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma. Hepatology 2008; 47:1223–1232 [View Article]
     [Google Scholar]
  32. Volinia S, Calin GA, Liu C-G, Ambs S, Cimmino A et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006; 103:2257–2261 [View Article]
     [Google Scholar]
  33. Agirre X, Jiménez-Velasco A, San José-Enériz E, Garate L, Bandrés E et al. Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res 2008; 6:1830–1840 [View Article][PubMed]
     [Google Scholar]
  34. Jongen-Lavrencic M, Sun SM, Dijkstra MK, Valk PJ, Löwenberg B. MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 2008; 111:5078–5085 [View Article][PubMed]
     [Google Scholar]
  35. Stadthagen G, Tehler D, Høyland-Kroghsbo NM, Wen J, Krogh A et al. Loss of miR-10a activates Ipo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice. PLoS Genet 2013; 9:e1003913 [View Article][PubMed]
     [Google Scholar]
  36. Hassel D, Cheng P, White MP, Ivey KN, Kroll J et al. MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling. Circ Res 2012; 111:1421–1433 [View Article]
     [Google Scholar]
  37. Feldman ER, Kara M, Coleman CB, Grau KR, Oko LM et al. Virus-encoded microRNAs facilitate gammaherpesvirus latency and pathogenesis in vivo . MBio 2014; 5:e00981-14 [View Article][PubMed]
     [Google Scholar]
  38. Akopian D, Shen K, Zhang X, Shan SO. Signal recognition particle: an essential protein-targeting machine. Annu Rev Biochem 2013; 82:693–721 [View Article][PubMed]
     [Google Scholar]
  39. Mary C, Scherrer A, Huck L, Lakkaraju AK, Thomas Y et al. Residues in SRP9/14 essential for elongation arrest activity of the signal recognition particle define a positively charged functional domain on one side of the protein. RNA 2010; 16:969–979 [View Article][PubMed]
     [Google Scholar]
  40. Ivanova E, Berger A, Scherrer A, Alkalaeva E, Strub K. Alu RNA regulates the cellular pool of active ribosomes by targeted delivery of SRP9/14 to 40S subunits. Nucleic Acids Res 2015; 43:2874–2887 [View Article]
     [Google Scholar]
  41. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116:281–297[PubMed] [Crossref]
     [Google Scholar]
  42. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 2010; 79:351–379 [View Article]
     [Google Scholar]
  43. Beckman JD, Chen C, Nguyen J, Thayanithy V, Subramanian S et al. Regulation of heme oxygenase-1 protein expression by miR-377 in combination with miR-217. J Biol Chem 2011; 286:3194–3202 [View Article][PubMed]
     [Google Scholar]
  44. Wensvoort G, Terpstra C, Pol JM, Ter Laak EA, Bloemraad M et al. Mystery swine disease in the Netherlands: the isolation of Lelystad virus. Vet Q 1991; 13:121–130 [View Article][PubMed]
     [Google Scholar]
  45. Zhang A, Zhao L, Li N, Duan H, Liu H et al. Carbon monoxide inhibits porcine reproductive and respiratory syndrome virus replication by the cyclic GMP/protein kinase G and NF-κB signaling pathway. J Virol 2017; 91:e01866-16 [View Article][PubMed]
     [Google Scholar]
  46. Li N, Du T, Yan Y, Zhang A, Gao J et al. MicroRNA let-7f-5p inhibits porcine reproductive and respiratory syndrome virus by targeting MYH9. Sci Rep 2016; 6:34332 [View Article][PubMed]
     [Google Scholar]
  47. Varkonyi-Gasic E, Hellens RP. Quantitative stem-loop RT-PCR for detection of microRNAs. Methods Mol Biol 2011; 744:145–157 [View Article][PubMed]
     [Google Scholar]
  48. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005; 33:e179 [View Article][PubMed]
     [Google Scholar]
  49. Wang C, Huang B, Kong N, Li Q, Ma Y et al. A novel porcine reproductive and respiratory syndrome virus vector system that stably expresses enhanced green fluorescent protein as a separate transcription unit. Vet Res 2013; 44:104 [View Article]
     [Google Scholar]
  50. Xiao S, Wang Q, Gao J, Wang L, He Z et al. Inhibition of highly pathogenic PRRSV replication in MARC-145 cells by artificial microRNAs. Virol J 2011; 8:491 [View Article]
     [Google Scholar]
  51. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R. Fast and effective prediction of microRNA/target duplexes. RNA 2004; 10:1507–1517 [View Article]
     [Google Scholar]
  52. 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]
  53. Betel D, Wilson M, Gabow A, Marks DS, Sander C. The microRNA.org resource: targets and expression. Nucleic Acids Res 2008; 36:D149–D153 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000708
Loading
Cellular microRNA miR-10a-5p inhibits replication of porcine reproductive and respiratory syndrome virus by targeting the host factor signal recognition particle 14
J. Gen. Virol. 98, 624 (2017); https://doi.org/10.1099/jgv.0.000708
/content/journal/jgv/10.1099/jgv.0.000708
/content/journal/jgv/10.1099/jgv.0.000708
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error