A virally-encoded tRNA neutralizes the PARIS antiviral defence system (2024)

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Abstract Access options Additional access options: Similar content being viewed by others Architecture and activation mechanism of the bacterial PARIS defence system Structural basis of Gabija anti-phage defence and viral immune evasion Viruses inhibit TIR gcADPR signalling to overcome bacterial defence Author information Authors and Affiliations Corresponding authors Supplementary information Supplementary Information Reporting Summary Supplementary Figure 1 Peer Review file Supplemental Video 1 Supplemental Video 2 Rights and permissions About this article Cite this article Comments References

Abstract

Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB)2. However, the mechanism by which AriA and AriB function in phage defense is unknown. Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving host tRNALys. Phage T5 subverts PARIS immunity through expression of a tRNALys variant that is not cleaved by PARIS, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids3.

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Similar content being viewed by others

A virally-encoded tRNA neutralizes the PARIS antiviral defence system (1)

Architecture and activation mechanism of the bacterial PARIS defence system

Article 07 August 2024

A virally-encoded tRNA neutralizes the PARIS antiviral defence system (2)

Structural basis of Gabija anti-phage defence and viral immune evasion

Article Open access 22 November 2023

A virally-encoded tRNA neutralizes the PARIS antiviral defence system (3)

Viruses inhibit TIR gcADPR signalling to overcome bacterial defence

Article 29 September 2022

Author information

Author notes

  1. Unaffiliated

  2. These authors contributed equally: Nathaniel Burman, Svetlana Belukhina, Florence Depardieu

Authors and Affiliations

  1. Montana State University, Bozeman, Department of Microbiology and Cell Biology, Bozeman, Montana, USA

    Nathaniel Burman,Royce A. Wilkinson,Andrew Santiago-Frangos,Ava B. Graham,Trevor Zahl,William S. Henriques,Murat Buyukyoruk&Blake Wiedenheft

  2. Institut Pasteur, Université Paris Cité, CNRS UMR 6047, Synthetic Biology, Paris, France

    Florence Depardieu,Christophe Rouillon,Baptiste Saudemont&David Bikard

  3. Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia

    Alexei Livenskyi&Konstantin Severinov

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  4. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia

    Alexei Livenskyi

  5. Peter the Great St Petersburg State Polytechnic University, St. Petersburg, Russia

    Natalia Morozova

  6. Department of Experimental Medical Science, Lund University, Lund, Sweden

    Lena Shyrokova,Tatsuaki Kurata&Vasili Hauryliuk

  7. Virus Centre, Lund University, Lund, Sweden

    Vasili Hauryliuk

  8. Science for Life Laboratory, Lund, Sweden

    Vasili Hauryliuk

  9. Waksman Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA

    Konstantin Severinov

  10. Institut Pasteur, CNRS UMR 3525, Université Paris Cité, Unité Régulation Spatiale des Génomes, Paris, France

    Justine Groseille,Agnès Thierry&Romain Koszul

  11. Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, Paris, France

    Justine Groseille

  12. Sorbonne Université, Collège Doctoral, Paris, France

    Justine Groseille

  13. Institut Pasteur, Université Paris Cité, Molecular Diversity of Microbes, Paris, France

    Florian Tesson&Aude Bernheim

Authors

  1. Nathaniel Burman

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  2. Svetlana Belukhina

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  3. Florence Depardieu

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  4. Royce A. Wilkinson

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  5. Mikhail Skutel

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  6. Andrew Santiago-Frangos

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  7. Ava B. Graham

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  8. Alexei Livenskyi

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  10. Natalia Morozova

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  11. Trevor Zahl

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  12. William S. Henriques

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  13. Murat Buyukyoruk

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  14. Christophe Rouillon

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  15. Baptiste Saudemont

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  16. Lena Shyrokova

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  17. Tatsuaki Kurata

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  18. Vasili Hauryliuk

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  19. Konstantin Severinov

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  20. Justine Groseille

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  21. Agnès Thierry

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  22. Romain Koszul

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  23. Florian Tesson

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  24. Aude Bernheim

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  25. David Bikard

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  26. Blake Wiedenheft

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  27. Artem Isaev

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Corresponding authors

Correspondence to David Bikard or Blake Wiedenheft.

Supplementary information

Supplementary Information

This file contains Supplementary Tables 1-3 and legends for Supplementary Videos.

Supplementary Figure 1

Uncropped images.

Supplemental Video 1

Visualization of PARIS. Masked local refinement was used to generate a high-resolution map of one asymmetric unit (AriA2:AriB1). Density for ATPγS is evident in both nucleotide binding domains (NBDs) of the AriA homodimer. A series of electrostatic interactions link AriB to AriA. AriB is located directly above the NDBs of AriA. Catalytic residues in TOPRIM domain are conserved. Focused 3-D classification was used to isolate two isomers of the assembled complex, a ‘cis’ arrangement and a ‘trans’ arrangement. Viral triggers of PARIS, such as the T7 Ocr protein, release AriB from the complex which forms a homodimeric nuclease that cleaves host tRNALys.

Supplemental Video 2

Ocr induces membrane permeability in cells expressing the PARIS immune system. Time course video demonstrating PARIS-induced membrane permeability by propidium iodide staining. The cells turn red within 30 minutes of Ocr induction.

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A virally-encoded tRNA neutralizes the PARIS antiviral defence system (4)

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Burman, N., Belukhina, S., Depardieu, F. et al. A virally-encoded tRNA neutralizes the PARIS antiviral defence system. Nature (2024). https://doi.org/10.1038/s41586-024-07874-3

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  • DOI: https://doi.org/10.1038/s41586-024-07874-3

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A virally-encoded tRNA neutralizes the PARIS antiviral defence system (2024)

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