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Host genome integration and giant virus-induced reactivation of the virophage mavirus

Nature volume 540, pages 288291 (08 December 2016) | Download Citation

Abstract

Endogenous viral elements are increasingly found in eukaryotic genomes1, yet little is known about their origins, dynamics, or function. Here we provide a compelling example of a DNA virus that readily integrates into a eukaryotic genome where it acts as an inducible antiviral defence system. We found that the virophage mavirus2, a parasite of the giant Cafeteria roenbergensis virus (CroV)3, integrates at multiple sites within the nuclear genome of the marine protozoan Cafeteria roenbergensis4. The endogenous mavirus is structurally and genetically similar to eukaryotic DNA transposons and endogenous viruses of the Maverick/Polinton family5,6,7. Provirophage genes are not constitutively expressed, but are specifically activated by superinfection with CroV, which induces the production of infectious mavirus particles. Virophages can inhibit the replication of mimivirus-like giant viruses and an anti-viral protective effect of provirophages on their hosts has been hypothesized2,8. We find that provirophage-carrying cells are not directly protected from CroV; however, lysis of these cells releases infectious mavirus particles that are then able to suppress CroV replication and enhance host survival during subsequent rounds of infection. The microbial host–parasite interaction described here involves an altruistic aspect and suggests that giant-virus-induced activation of provirophages might be ecologically relevant in natural protist populations.

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Acknowledgements

This research was supported by the Max Planck Society. We are grateful to C. Suttle for access to host and virus strains, and to the Roscoff team for maintaining and distributing protist strains. We thank K.-A. Seifert, K. Fenzl and K. Barenhoff for technical assistance, U. Mersdorf for electron microscopy, C. Roome for IT support, L. Czaja and the Max Planck Genome Centre in Cologne for bioinformatic assistance, S. Higgins for suggestions, K. Haslinger and J. Reinstein for comments on the manuscript, and I. Schlichting for mentoring and support.

Author information

Author notes

    • Thomas Hackl

    Present address: Massachusetts Institute of Technology, 15 Vassar Street, Cambridge, Massachusetts 02139, USA.

Affiliations

  1. Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, 69120 Heidelberg, Germany

    • Matthias G. Fischer
    •  & Thomas Hackl

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Contributions

M.G.F. conceived the study, designed and performed experiments, collected, analysed, and interpreted data, and wrote the manuscript. T.H. corrected and assembled sequence data, and analysed, interpreted, and visualized data. Both authors revised and approved the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Matthias G. Fischer.

Reviewer Information

Nature thanks J.-M. Claverie, E. Koonin and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature20593

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