Letter | Published:

MIMIVIRE is a defence system in mimivirus that confers resistance to virophage

Nature volume 531, pages 249252 (10 March 2016) | Download Citation

Abstract

Since their discovery, giant viruses have revealed several unique features that challenge the conventional definition of a virus, such as their large and complex genomes, their infection by virophages and their presence of transferable short element transpovirons1,2,3,4,5. Here we investigate the sensitivity of mimivirus to virophage infection in a collection of 59 viral strains and demonstrate lineage specificity in the resistance of mimivirus to Zamilon6, a unique virophage that can infect lineages B and C of mimivirus but not lineage A. We hypothesized that mimiviruses harbour a defence mechanism resembling the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system that is widely present in bacteria and archaea7,8,9,10. We performed de novo sequencing of 45 new mimivirus strains and searched for sequences specific to Zamilon in a total of 60 mimivirus genomes. We found that lineage A strains are resistant to Zamilon and contain the insertion of a repeated Zamilon sequence within an operon, here named the ‘mimivirus virophage resistance element’ (MIMIVIRE). Further analyses of the surrounding sequences showed that this locus is reminiscent of a defence mechanism related to the CRISPR–Cas system. Silencing the repeated sequence and the MIMIVIRE genes restores mimivirus susceptibility to Zamilon. The MIMIVIRE proteins possess the typical functions (nuclease and helicase) involved in the degradation of foreign nucleic acids. The viral defence system, MIMIVIRE, represents a nucleic-acid-based immunity against virophage infection.

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Acknowledgements

We thank S. Benamar, A. Caputo and C. Robert for technical support, and L. Pinault for her assistance on protein production.

Author information

Author notes

    • Anthony Levasseur
    •  & Meriem Bekliz

    These authors contributed equally to this work.

Affiliations

  1. Aix-Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), UM63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France

    • Anthony Levasseur
    • , Meriem Bekliz
    • , Eric Chabrière
    • , Bernard La Scola
    •  & Didier Raoult
  2. IHU Méditerranée Infection, Pôle des Maladies Infectieuses, Assistance Publique-Hôpitaux de Marseille, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France

    • Anthony Levasseur
    • , Meriem Bekliz
    • , Eric Chabrière
    • , Bernard La Scola
    •  & Didier Raoult
  3. Aix-Marseille Université, CNRS, Centrale Marseille, I2M, UMR7373, FR 4213 - FR Eccorev 3098, équipe EBM, 13331 Marseille, France

    • Pierre Pontarotti

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Contributions

A.L., B.L. and D.R. conceived the project and designed the study and experiments; A.L., M.B., P.P., B.L. and D.R. analysed the results; A.L. and D.R. wrote the manuscript. All authors read and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Bernard La Scola or Didier Raoult.

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https://doi.org/10.1038/nature17146

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