Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Progress
  • Published:

New roles for large and small viral RNAs in evading host defences

Nature Reviews Genetics volume 9, pages 503–507 (2008)Cite this article

Abstract

It has been known for decades that some clinically important viruses encode abundant amounts of non-coding RNAs (ncRNAs) during infection. Until recently, the number of viral ncRNAs identified was few and their functions were mostly unknown. Although our understanding is still in its infancy, several recent reports have identified new functions for viral microRNAs and larger ncRNAs. These results so far show that different classes of viral ncRNAs act to autoregulate viral gene expression and evade host antiviral defences such as apoptosis and the immune response.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Functions of viral non-coding RNAs in evading host defences.

Similar content being viewed by others

References

  1. Birney, E. et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799–816 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Carninci, P. et al. The transcriptional landscape of the mammalian genome. Science 309, 1559–1563 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Maeda, N. et al. Transcript annotation in FANTOM3: mouse gene catalog based on physical cDNAs PLoS Genet. 2, e62 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mattick, J. S. & Makunin, I. V. Non-coding RNA. Hum. Mol. Genet. 15, R17–R29 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Pfeffer, S. et al. Identification of virus-encoded microRNAs. Science 304, 734–736 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Griffiths-Jones, S. miRBase: the microRNA sequence database. Methods Mol. Biol. 342, 129–138 (2006).

    CAS  PubMed  Google Scholar 

  7. Lodoen, M. B. & Lanier, L. L. Viral modulation of NK cell immunity. Nature Rev. Microbiol. 3, 59–69 (2005).

    Article  CAS  Google Scholar 

  8. Stern-Ginossar, N. et al. Host immune system gene targeting by a viral miRNA. Science 317, 376–381 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dunn, C. et al. Human cytomegalovirus glycoprotein UL16 causes intracellular sequestration of NKG2D ligands, protecting against natural killer cell cytotoxicity. J. Exp. Med. 197, 1427–1439 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gottwein, E. et al. A viral microRNA functions as an orthologue of cellular miR-155. Nature 450, 1096–1099 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Skalsky, R. L. et al. Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. J. Virol. 81, 12836–12845 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nair, V. & Zavolan, M. Virus-encoded microRNAs: novel regulators of gene expression. Trends Microbiol. 14, 169–175 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Sullivan, C. S. et al. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 435, 682–686 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Grey, F. et al. A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication. PLoS Pathog. 3, e163 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lo, A. K. et al. Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Natl Acad. Sci. USA 104, 16164–16169 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pfeffer, S. et al. Identification of microRNAs of the herpesvirus family. Nature Methods 2, 269–276 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Mathews, M. B. & Shenk, T. Adenovirus-associated RNA and translation control. J. Virol. 65, 5657–5662 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Fok, V. Friend, K. & Steitz, J. A. Epstein–Barr virus noncoding RNAs are confined to the nucleus, whereas their partner, the human La protein, undergoes nucleocytoplasmic shuttling. J. Cell Biol. 173, 319–325 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ruf, I. K. et al. Protection from interferon-induced apoptosis by Epstein–Barr virus small RNAs is not mediated by inhibition of PKR. J. Virol. 79, 14562–14569 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Reeves, M. B. et al. Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 316, 1345–1348 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Burnside, J. et al. Marek's disease virus encodes microRNAs that map to meq and the latency-associated transcript. J. Virol. 80, 8778–8786 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lu, S. & Cullen, B. R. Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis. J. Virol. 78, 12868–12876 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xu, N. et al. Adenovirus virus-associated RNAII-derived small RNAs are efficiently incorporated into the RNA-induced silencing complex and associate with polyribosomes. J. Virol. 81, 10540–10549 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Higgins, G. D. et al. Presence and distribution of human papillomavirus sense and antisense RNA transcripts in genital cancers. J. Gen. Virol. 72, 885–895 (1991).

    Article  CAS  PubMed  Google Scholar 

  25. Liu, Z., Batt, D. B. & Carmichael, G. G. Targeted nuclear antisense RNA mimics natural antisense-induced degradation of polyoma virus early RNA. Proc. Natl Acad. Sci. USA 91, 4258–4262 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lukac, D. M., Kirshner, J. R. & Ganem, D. Transcriptional activation by the product of open reading frame 50 of Kaposi's sarcoma-associated herpesvirus is required for lytic viral reactivation in B cells. J. Virol. 73, 9348–9361 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Prang, N., Wolf, H. & Schwarzmann, F. Latency of Epstein–Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1. J. Med. Virol. 59, 512–519 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Zhang, G. et al. Antisense transcription in the human cytomegalovirus transcriptome. J. Virol. 81, 11267–11281 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yu, W. et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451, 202–206 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cook, H. L. et al. Small nuclear RNAs encoded by herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells. Curr. Biol. 15, 974–979 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Ambros, V. The functions of animal microRNAs. Nature 431, 350–355 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Du, T. & Zamore, P. D. microPrimer: the biogenesis and function of microRNA. Development 132, 4645–4652 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Yekta, S., Shih, I. H. & Bartel, D. P. MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594–596 (2004).

    CAS  PubMed  Google Scholar 

  34. Mansfield, J. H. et al. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genet. 36, 1079–1083 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Vasudevan, S., Tong, Y. & Steitz, J. A. Switching from repression to activation: microRNAs can up-regulate translation. Science 318, 1931–1934 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Kim, V. N. MicroRNA biogenesis: coordinated cropping and dicing. Nature Rev. Mol. Cell Biol. 6, 376–385 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Thanks to the members and friends of the Sullivan laboratory for comments regarding this manuscript. Research in the Sullivan laboratory is supported by University of Texas (UT) at Austin start-up funds and a UT Austin Institute for Cellular and Molecular Biology Research Fellowship.

Author information

Authors and Affiliations

  1. Christopher S. Sullivan is at The University of Texas, Molecular Genetics & Microbiology, 1 University Station A5000, Austin, Texas 78712-0162, USA. chris_sullivan@mail.utexas.edu,

    Christopher S. Sullivan

Authors
  1. Christopher S. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

FURTHER INFORMATION

Christopher Sullivan's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sullivan, C. New roles for large and small viral RNAs in evading host defences. Nat Rev Genet 9, 503–507 (2008). https://doi.org/10.1038/nrg2349

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg2349

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing