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.

  • Correspondence
  • Published:

Questioning antiviral RNAi in mammals

Nature Microbiology volume 2, Article number: 17052 (2017) Cite this article

Subjects

To the Editor — I wish to comment on the central claim made in the article by Li et al., which suggests that mammals elicit a small RNA-mediated response to RNA virus infection in somatic cells1. While our evolutionary past certainly suggests that our ancestors used RNA interference (RNAi) to limit virus replication, with the emergence of vertebrates came a protein-based defence that hinged on the family of interferons (IFNs)2. A question that remains is whether RNAi still represents a physiological component of our cellular antiviral arsenal that works alongside the IFN system.

Over the past three years, four papers (two from Maillard et al. and two from Li et al.) have reported on observations that provide some support for the idea that RNAi contributes to the mammalian antiviral arsenal1,3–5. In 2013, Maillard et al. published a study that suggested that pluripotent stem cells retained the capacity to elicit an RNAi response3. This claim supported earlier work that found, unlike somatic cells, multipotent lineages such as stem cells could process double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs)6,7. In a second paper published back-to-back with Maillard et al., Li et al. demonstrated an inverse correlation between the appearance of viral small RNAs and virus replication in suckling mice5. While not addressed directly, this later study suggested that RNAi could also be detected in somatic cells, although this seemingly contradicted the work by Maillard et al., which showed RNAi was lost in differentiated cells8. More recently, a follow-up paper by Maillard et al. demonstrated that RNAi could be observed in differentiated cells only when they were void of a canonical IFN response4. As both stem cells and newborn mice have deficiencies in IFN, it seemed that a consensus for the longstanding controversy concerning RNAi in mammals would finally be reached — RNAi in mammals may be observable but only in small subpopulations of cells that are IFN-nonresponsive. However, even this idea, which itself still requires independent corroboration, has now been called into question with the most recent conclusions of Li et al. suggesting that mammalian RNAi is readily detectable in IFN-competent somatic cells1.

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

References

  1. Li, Y. et al. Nat. Microbiol. 2, 16250 (2016).

    Article  CAS  Google Scholar 

  2. tenOever, B. R. Cell Host Microbe 19, 142–149 (2016).

    Article  CAS  Google Scholar 

  3. Maillard, P. V. et al. Science 342, 235–238 (2013).

    Article  CAS  Google Scholar 

  4. Maillard, P. V. et al. EMBO J. 35, 2505–2518 (2016).

    Article  CAS  Google Scholar 

  5. Li, Y., Lu, J., Han, Y., Fan, X. & Ding, S. W. Science 342, 231–234 (2013).

    Article  CAS  Google Scholar 

  6. Billy, E., Brondani, V., Zhang, H., Müller, U. & Filipowicz, W. Proc. Natl Acad. Sci. USA 98, 14428–14433 (2001).

    Article  CAS  Google Scholar 

  7. Paddison, P. J., Caudy, A. A. & Hannon, G. J. Proc. Natl Acad. Sci. USA 99, 1443–1448 (2002).

    Article  CAS  Google Scholar 

  8. Cullen, B. R., Cherry, S. & tenOever, B. R. Cell Host Microbe 14, 374–378 (2013).

    Article  CAS  Google Scholar 

  9. Seo, G. J. et al. Cell Host Microbe 14, 435–445 (2013).

    Article  CAS  Google Scholar 

  10. Bogerd, H. P. et al. J. Virol. 88, 8065–8076 (2014).

    Article  Google Scholar 

  11. Benitez, A. A., Spanko, L. A., Bouhaddou, M., Sachs, D. & tenOever, B. R. Cell Rep. 13, 1456–1466 (2015).

    Article  CAS  Google Scholar 

  12. Backes, S. et al. Cell Rep. 8, 114–125 (2014).

    Article  CAS  Google Scholar 

  13. García-Sastre, A. et al. Virology 252, 324–330 (1998).

    Article  Google Scholar 

  14. Bucher, E., Hemmes, H., de Haan, P., Goldbach, R. & Prins, M. J. Gen. Virol. 85, 983–991 (2004).

    Article  CAS  Google Scholar 

  15. Li, W. X. et al. Proc. Natl Acad. Sci. USA 101, 1350–1355 (2004).

    Article  CAS  Google Scholar 

  16. Kennedy, E. M. et al. Proc. Natl Acad. Sci. USA 112, E6945–E6954 (2015).

    Article  CAS  Google Scholar 

  17. Shapiro, J. S. et al. Proc. Natl Acad. Sci. USA 111, 7108–7113 (2014).

    Article  CAS  Google Scholar 

  18. Shapiro, J. S., Langlois, R. A., Pham, A. M. & tenOever, B. R. RNA 18, 1338–1346 (2012).

    Article  CAS  Google Scholar 

  19. Shapiro, J. S., Varble, A., Pham, A. M. & tenOever, B. R. RNA 16, 2068–2074 (2010).

    Article  CAS  Google Scholar 

  20. O’Carroll, D. et al. Genes Dev. 21, 1999–2004 (2007).

    Article  Google Scholar 

  21. Aguado, L. C. et al. Cell Host Microbe 18, 714–722 (2015).

    Article  CAS  Google Scholar 

  22. Girardi, E. et al. Sci. Rep. 5, 10693 (2015).

    Article  Google Scholar 

  23. Kok, K. H. & Jin, D. Y. J. Gen. Virol. 87, 2639–2644 (2006).

    Article  CAS  Google Scholar 

  24. Perez, J. T. et al. Nat. Biotechnol. 27, 572–576 (2009).

    Article  CAS  Google Scholar 

  25. Langlois, R. A. et al. Nat. Biotechnol. 31, 844–847 (2013).

    Article  CAS  Google Scholar 

  26. Langlois, R. A., Varble, A., Chua, M. A., García-Sastre, A. & tenOever, B. R. Proc. Natl Acad. Sci. USA 109, 12117–12122 (2012).

    Article  CAS  Google Scholar 

  27. Varble, A. et al. Proc. Natl Acad. Sci. USA 107, 11519–11524 (2010).

    Article  CAS  Google Scholar 

  28. Benitez, A. A. et al. Cell Rep. 11, 1714–1726 (2015).

    Article  CAS  Google Scholar 

  29. Popper, K. R. The Logic of Scientific Discovery (Martino Fine Books, 2014).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA

    Benjamin R. tenOever

Authors
  1. Benjamin R. tenOever
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin R. tenOever.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

tenOever, B. Questioning antiviral RNAi in mammals. Nat Microbiol 2, 17052 (2017). https://doi.org/10.1038/nmicrobiol.2017.52

Download citation

  • Published:

  • DOI: https://doi.org/10.1038/nmicrobiol.2017.52

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