Skip to main content

Advertisement

Log in

Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by hcmv-miR-UL36

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small RNAs, 19–23 nucleotides in length, which regulate a variety of cellular processes. Human cytomegalovirus (HCMV) encodes only one intronic miRNA: human cytomegalovirus microRNA UL36 (hcmv-miR-UL36). In this study, we found that over-expression of hcmv-miR-UL36 resulted in a more than threefold increase in HCMV DNA synthesis at 24 h post infection. Fifteen putative targets of hcmv-miR-UL36 were identified using hybrid PCR, one being the HCMV UL138 gene that has previously been identified as a novel latency-associated determinant of HCMV infection. Down-regulation of UL138 expression by hcmv-miR-UL36 was validated using luciferase reporter assays and Western blot analysis in HEK293 cells. In the presence of hcmv-miR-UL36, we observed a 74.6% decrease in luciferase activity and a 46.2% decrease in HCMV UL138 protein expression. Our results indicate that hcmv-miR-UL36 may be a viral miRNA contributing to HCMV replication.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Ambros V 2004 The functions of animal microRNAs. Nature 431 350–355

    Article  PubMed  CAS  Google Scholar 

  • Brennecke J, Hipfner DR, Stark A, Russel RB and Cohen SM 2003 Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113 25–36

    Article  PubMed  CAS  Google Scholar 

  • Cha TA, Tom E, Kemble GW, Duke GM, Mocarski ES and Spaete RR 1996 Human cytomegalovirus clinical isolates carry at least 19 genes not found in laboratory strains. J. Virol. 70 78–83

    PubMed  CAS  Google Scholar 

  • Crough T and Khanna R 2009 Immunobiology of human cytomegalovirus: from bench to bedside. Clin. Microbiol. Rev. 22 76–98

    Article  PubMed  CAS  Google Scholar 

  • Dolan A, Cunningham C and Hector RD 2004 Genetic content of wild-type human cytomegalovirus. J. Gen. Virol. 85 1301–1312

    Article  PubMed  CAS  Google Scholar 

  • Dostie J, Mourelatos Z, Yang M, Sharma A and Dreyfuss G 2003 Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 9 180–186

    Article  PubMed  CAS  Google Scholar 

  • Dunn W, Trang P, Zhong Q, Yang E, van Belle C and Liu F 2005 Human cytomegalovirus expresses novel microRNAs during productive viral infection. Cell. Microbiol. 7 1684–1695

    Article  PubMed  CAS  Google Scholar 

  • Gebert S, Schmolke S, Sorg G, Flöss S, Plachter B and Stamminger T 1997 The UL84 protein of human cytomegalovirus acts as a transdominant inhibitor of immediate-early-mediated transactivation that is able to prevent viral replication. J. Virol. 71 7048–7060

    PubMed  CAS  Google Scholar 

  • Goodrum F, Reeves M, Sinclair J, High K and Shenk T 2007 Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro. Blood 110 937–945

    Article  PubMed  CAS  Google Scholar 

  • Grey F, Antoniewicz A, Allen E, Saugstad J, McShea A, Carrington JC and Nelson J 2005 Identification and characterization of human cytomegalovirus-encoded microRNAs. J. Virol. 79 12095–12099

    Article  PubMed  CAS  Google Scholar 

  • Grey F, Meyers H, White EA, Spector DH and Nelson J 2007 A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication. PLoS Pathog. 3 e163

    Article  PubMed  Google Scholar 

  • Grey F, Tirabassi R, Meyers H, Wu G, McWeeney S, Hook L and Nelson JA 2010 A viral microRNA down-regulates multiple cell cycle genes through mRNA 5'UTRs. PLoS Pathog. 6 e1000967

    Article  PubMed  Google Scholar 

  • Huang Y, Qi Y, Ruan Q, Ma Y, He R, Ji Y and Sun Z 2011 A rapid method to screen putative mRNA targets of any known microRNA. Virol. J. 8 8

    Article  PubMed  CAS  Google Scholar 

  • Filipowicz W 2005 RNAi: the nuts and bolts of the RISC machine. Cell 122 17–20

    Article  PubMed  CAS  Google Scholar 

  • Ho M 1990 Epidemiology of cytomegalovirus infections. Rev. Infect. Dis. 12 S701–S710

    Article  PubMed  Google Scholar 

  • Khoshnevis M 2002 Cytomegalovirus infections. Dermatol. Clin. 20 291–299

    Article  PubMed  Google Scholar 

  • Petrucelli A, Rak M, Grainger L and Goodrum F 2009 Characterization of a novel golgi apparatus-localized latency determinant encoded by human cytomegalovirus. J. Virol. 83 5615–5629

    Article  PubMed  CAS  Google Scholar 

  • Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M and Tuschl T 2005 Identification of microRNAs of the herpesvirus family. Nat. Methods 2 269–276

    Article  PubMed  CAS  Google Scholar 

  • Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR and Ruvkun G 2000 The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403 901–906

    Article  PubMed  CAS  Google Scholar 

  • Staras SA, Dollard SC, Radford KW, Flanders WD, Pass RF and Cannon MJ 2006 Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin. Infect. Dis. 43 1143–1151

    Article  PubMed  Google Scholar 

  • Stark TJ, Arnold JD, Spector DH and Yeo GW 2012 High-resolution profiling and analysis of viral and host small RNAs during human cytomegalovirus infection. J. Virol. 86 226–235

    Article  PubMed  CAS  Google Scholar 

  • Stern-Ginossar N, Saleh N, Goldberg MD, Prichard M, Wolf DG and Mandelboim O 2009 Analysis of human cytomegalovirus-encoded microRNA activity during infection. J. Virol. 83 10684–10693

    Article  PubMed  CAS  Google Scholar 

  • Whitman AG, Bryan BA, Dyson OF, Patel DK, Ramasamy D, Anantharaman S, Reber AJ and Akula SM 2005 AIDS related viruses, their association with leukemia, and Raf signaling. Curr. HIV Res. 3 319–327

    Article  PubMed  CAS  Google Scholar 

  • Xu P, Vernooy SY, Guo M and Hay BA 2003 The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr. Biol. 13 790–795

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Cei SA, Huete AR and Pari GS 2004 Human cytomegalovirus UL84 insertion mutant defective for viral DNA synthesis and growth. J Virol. 78 10360–10369

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81171580 and 81201274), the Specialized Research Fund for the Doctoral Program of Higher Education (20112104110012) and the Outstanding Scientific Fund of Shengjing Hospital.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qiang Ruan.

Additional information

Corresponding editor: Shahid Jameel

MS received 22 March 2013; accepted 28 June 2013

Corresponding editor: Shahid Jameel

[Huang Y, Qi Y, Ma Y, He R, Ji Y, Sun Z and Ruan Q 2013 Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by hcmv-miR-UL36. J. Biosci. 38 1–7] DOI 10.1007/s12038-013-9353-4

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, Y., Qi, Y., Ma, Y. et al. Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by hcmv-miR-UL36. J Biosci 38, 479–485 (2013). https://doi.org/10.1007/s12038-013-9353-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-013-9353-4

Keywords

Navigation