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.

  • Perspective
  • Published:

Resident viruses and their interactions with the immune system

Nature Immunology volume 14, pages 654–659 (2013) Cite this article

View saved research

Abstract

The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human 'virobiota' and its associated genes (the 'virome'), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota–immune system interactions for human health.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

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

Figure 1: Anatomical locations of resident viruses in humans.
Figure 2: Pathogenic viral infection results in the expansion of the enteric virobiota.
Figure 3: Model for bacteriophage recognition by antiviral innate immune sensors.

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news in related subjects.

References

  1. Hooper, L.V., Littman, D.R. & Macpherson, A.J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 489, 220–230 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. White, D.W., Suzanne Beard, R. & Barton, E.S. Immune modulation during latent herpesvirus infection. Immunol. Rev. 245, 189–208 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Handley, S.A. et al. Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome. Cell 151, 253–266 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Reyes, A. et al. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466, 334–338 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Minot, S. et al. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res. 21, 1616–1625 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Foulongne, V. et al. Human skin microbiota: high diversity of DNA viruses identified on the human skin by high throughput sequencing. PLoS ONE 7, e38499 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang, T. et al. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol. 4, e3 (2006).

    Article  PubMed  CAS  Google Scholar 

  9. Turnbaugh, P.J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Pride, D.T. et al. Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome. ISME J. 6, 915–926 (2012).

    Article  CAS  PubMed  Google Scholar 

  11. Breitbart, M. et al. Viral diversity and dynamics in an infant gut. Res. Microbiol. 159, 367–373 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Weinbauer, M.G. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28, 127–181 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. DeMarini, D.M. & Lawrence, B.K. Prophage induction by DNA topoisomerase II poisons and reactive-oxygen species: role of DNA breaks. Mutat. Res. 267, 1–17 (1992).

    Article  CAS  PubMed  Google Scholar 

  14. Duerkop, B.A., Clements, C.V., Rollins, D., Rodrigues, J.L. & Hooper, L.V. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl. Acad. Sci. USA 109, 17621–17626 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kim, M.S., Park, E.J., Roh, S.W. & Bae, J.W. Diversity and abundance of single-stranded DNA viruses in human feces. Appl. Environ. Microbiol. 77, 8062–8070 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Canchaya, C., Fournous, G., Chibani-Chennoufi, S., Dillmann, M.L. & Brussow, H. Phage as agents of lateral gene transfer. Curr. Opin. Microbiol. 6, 417–424 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Pride, D.T., Salzman, J. & Relman, D.A. Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses. Environ. Microbiol. 14, 2564–2576 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ivanov, I.I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mazmanian, S.K., Liu, C.H., Tzianabos, A.O. & Kasper, D.L. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107–118 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Kuss, S.K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. USA 108, 5354–5359 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245–249 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schowalter, R.M., Pastrana, D.V., Pumphrey, K.A., Moyer, A.L. & Buck, C.B. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7, 509–515 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Miller, C.S., Avdiushko, S.A., Kryscio, R.J., Danaher, R.J. & Jacob, R.J. Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in saliva of healthy individuals after dental treatment. J. Clin. Microbiol. 43, 2173–2180 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lazarevic, V. et al. Analysis of the salivary microbiome using culture-independent techniques. J. Clin. Bioinforma. 2, 4 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bogaert, D. et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PLoS ONE 6, e17035 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nokso-Koivisto, J., Kinnari, T.J., Lindahl, P., Hovi, T. & Pitkaranta, A. Human picornavirus and coronavirus RNA in nasopharynx of children without concurrent respiratory symptoms. J. Med. Virol. 66, 417–420 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Minot, S., Grunberg, S., Wu, G.D., Lewis, J.D. & Bushman, F.D. Hypervariable loci in the human gut virome. Proc. Natl. Acad. Sci. USA 109, 3962–3966 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Victoria, J.G. et al. Metagenomic analyses of viruses in stool samples from children with acute flaccid paralysis. J. Virol. 83, 4642–4651 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Finkbeiner, S.R. et al. Metagenomic analysis of human diarrhea: viral detection and discovery. PLoS Pathog. 4, e1000011 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Lee, Y.K. & Mazmanian, S.K. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330, 1768–1773 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McFall-Ngai, M. Adaptive immunity: care for the community. Nature 445, 153 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Salzman, N.H. et al. Enteric defensins are essential regulators of intestinal microbial ecology. Nat. Immunol. 11, 76–83 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Lysholm, F. et al. Characterization of the viral microbiome in patients with severe lower respiratory tract infections, using metagenomic sequencing. PLoS ONE 7, e30875 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Willner, D. et al. Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS ONE 4, e7370 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Brandl, K. et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804–807 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Fukuda, S. et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469, 543–547 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Virgin, H.W., Wherry, E.J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30–50 (2009).

    Article  CAS  PubMed  Google Scholar 

  40. Barton, E.S. et al. Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447, 326–329 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Zuniga, E.I., Liou, L.Y., Mack, L., Mendoza, M. & Oldstone, M.B. Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections. Cell Host Microbe 4, 374–386 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Inchley, C.J. & Howard, J.G. The immunogenicity of phagocytosed T4 bacteriophage: cell replacement studies with splenectomized and irradiated mice. Clin. Exp. Immunol. 5, 189–198 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Nelson, J., Ormrod, D.J., Wilson, D. & Miller, T.E. Host immune status in uraemia III. Humoral response to selected antigens in the rat. Clin. Exp. Immunol. 42, 234–240 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Gorski, A. et al. Bacteriophages and transplantation tolerance. Transplant. Proc. 38, 331–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Eriksson, F. et al. Tumor-specific bacteriophages induce tumor destruction through activation of tumor-associated macrophages. J. Immunol. 182, 3105–3111 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. Mori, K., Kubo, T., Kibayashi, Y., Ohkuma, T. & Kaji, A. Anti-vaccinia virus effect of M13 bacteriophage DNA. Antiviral Res. 31, 79–86 (1996).

    Article  CAS  PubMed  Google Scholar 

  47. Duerr, D.M., White, S.J. & Schluesener, H.J. Identification of peptide sequences that induce the transport of phage across the gastrointestinal mucosal barrier. J. Virol. Methods 116, 177–180 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Hamzeh-Mivehroud, M., Mahmoudpour, A., Rezazadeh, H. & Dastmalchi, S. Non-specific translocation of peptide-displaying bacteriophage particles across the gastrointestinal barrier. Eur. J. Pharm. Biopharm. 70, 577–581 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Keller, R. & Engley, F.B. Jr. Fate of bacteriophage particles introduced into mice by various routes. Proc. Soc. Exp. Biol. Med. 98, 577–580 (1958).

    Article  CAS  PubMed  Google Scholar 

  50. Rescigno, M. et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2, 361–367 (2001).

    Article  CAS  PubMed  Google Scholar 

  51. Barfoot, R. et al. Some properties of dendritic macrophages from peripheral lymph. Immunology 68, 233–239 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Gorski, A. et al. Bacteriophage translocation. FEMS Immunol. Med. Microbiol. 46, 313–319 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Lepage, P. et al. Dysbiosis in inflammatory bowel disease: a role for bacteriophages? Gut 57, 424–425 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Yan, N. & Chen, Z.J. Intrinsic antiviral immunity. Nat. Immunol. 13, 214–222 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sun, L., Wu, J., Du, F., Chen, X. & Chen, Z.J. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339, 786–791 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Wu, J. et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339, 826–830 (2013).

    Article  CAS  PubMed  Google Scholar 

  57. Doulatov, S. et al. Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements. Nature 431, 476–481 (2004).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Supported by a Ruth L. Kirschstein National Research Service Award F32 DK089718 (to B.A.D.), The Howard Hughes Medical Institute (to L.V.H.), US National Institutes of Health grant R01 DK070855 (to L.V.H.) and a Burroughs Wellcome Foundation Investigators in the Pathogenesis of Infectious Diseases award (to L.V.H.).

Author information

Authors and Affiliations

  1. Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Breck A Duerkop & Lora V Hooper

  2. Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Lora V Hooper

  3. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Lora V Hooper

Authors
  1. Breck A Duerkop
    View author publications

    Search author on:PubMed Google Scholar

  2. Lora V Hooper
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Lora V Hooper.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Duerkop, B., Hooper, L. Resident viruses and their interactions with the immune system. Nat Immunol 14, 654–659 (2013). https://doi.org/10.1038/ni.2614

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/ni.2614

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