Letter | Published:

Herpesvirus latency confers symbiotic protection from bacterial infection

Nature volume 447, pages 326329 (17 May 2007) | Download Citation

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Abstract

All humans become infected with multiple herpesviruses during childhood. After clearance of acute infection, herpesviruses enter a dormant state known as latency. Latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease1. Here we show that herpesvirus latency also confers a surprising benefit to the host. Mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which are genetically highly similar to the human pathogens Epstein–Barr virus and human cytomegalovirus2, respectively, are resistant to infection with the bacterial pathogens Listeria monocytogenes and Yersinia pestis. Latency-induced protection is not antigen specific but involves prolonged production of the antiviral cytokine interferon-γ and systemic activation of macrophages. Latency thereby upregulates the basal activation state of innate immunity against subsequent infections. We speculate that herpesvirus latency may also sculpt the immune response to self and environmental antigens through establishment of a polarized cytokine environment. Thus, whereas the immune evasion capabilities and lifelong persistence of herpesviruses are commonly viewed as solely pathogenic, our data suggest that latency is a symbiotic relationship with immune benefits for the host.

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Acknowledgements

This research was supported by grants from the National Institutes of Health (E.S.B., V.L.M. & H.W.V.), an Abbott Scholar Award (D.W.W.) and a Cancer Research Institute postdoctoral fellowship (E.S.B.).

Author Contributions The original hypothesis of the article was formulated by E.S.B. and H.W.V. E.S.B. and D.W.W performed all experiments except those characterizing Y. pestis infection (J.S.C. and V.L.M.) and WNV infection (M.E. and M.S.D.). K.A.B.-M. made the initial observation of chronic IFNγ secretion during latency. The manuscript was written by E.S.B., D.W.W., and H.W.V. and all authors commented on data and conclusions prior to submission.

Author information

Author notes

    • Erik S. Barton

    Present address: Purdue University, Department of Biological Sciences, 915 W. State Street, West Lafayette, Indiana 47907, USA.

Affiliations

  1. Departments of Pathology and Immunology,

    • Erik S. Barton
    • , Douglas W. White
    • , Kelly A. Brett-McClellan
    • , Michael S. Diamond
    •  & Herbert W. Virgin IV
  2. Molecular Microbiology,

    • Jason S. Cathelyn
    • , Michael S. Diamond
    • , Virginia L. Miller
    •  & Herbert W. Virgin IV
  3. Medicine, and,

    • Michael Engle
    •  & Michael S. Diamond
  4. Pediatrics, and,

    • Virginia L. Miller
  5. Division of Rheumatology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA

    • Douglas W. White

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Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to Herbert W. Virgin IV.

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    Supplementary Figure

    This file contains Supplementary Figure S1 illustrating how latent infection with γHV68 or MCMV results in chronic, systemic macrophage activation.

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https://doi.org/10.1038/nature05762

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