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Prokaryotic viperins produce diverse antiviral molecules

Author

Listed:
  • Aude Bernheim

    (Weizmann Institute of Science)

  • Adi Millman

    (Weizmann Institute of Science)

  • Gal Ofir

    (Weizmann Institute of Science)

  • Gilad Meitav

    (Weizmann Institute of Science)

  • Carmel Avraham

    (Weizmann Institute of Science)

  • Helena Shomar

    (Pantheon Biosciences)

  • Masha M. Rosenberg

    (Pantheon Biosciences)

  • Nir Tal

    (Pantheon Biosciences)

  • Sarah Melamed

    (Weizmann Institute of Science)

  • Gil Amitai

    (Weizmann Institute of Science)

  • Rotem Sorek

    (Weizmann Institute of Science)

Abstract

Viperin is an interferon-induced cellular protein that is conserved in animals1. It has previously been shown to inhibit the replication of multiple viruses by producing the ribonucleotide 3′-deoxy-3′,4′-didehydro (ddh)-cytidine triphosphate (ddhCTP), which acts as a chain terminator for viral RNA polymerase2. Here we show that eukaryotic viperin originated from a clade of bacterial and archaeal proteins that protect against phage infection. Prokaryotic viperins produce a set of modified ribonucleotides that include ddhCTP, ddh-guanosine triphosphate (ddhGTP) and ddh-uridine triphosphate (ddhUTP). We further show that prokaryotic viperins protect against T7 phage infection by inhibiting viral polymerase-dependent transcription, suggesting that it has an antiviral mechanism of action similar to that of animal viperin. Our results reveal a class of potential natural antiviral compounds produced by bacterial immune systems.

Suggested Citation

  • Aude Bernheim & Adi Millman & Gal Ofir & Gilad Meitav & Carmel Avraham & Helena Shomar & Masha M. Rosenberg & Nir Tal & Sarah Melamed & Gil Amitai & Rotem Sorek, 2021. "Prokaryotic viperins produce diverse antiviral molecules," Nature, Nature, vol. 589(7840), pages 120-124, January.
    • Handle: RePEc:nat:nature:v:589:y:2021:i:7840:d:10.1038_s41586-020-2762-2
    DOI: 10.1038/s41586-020-2762-2
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    Cited by:

    1. Pedro Leão & Mary E. Little & Kathryn E. Appler & Daphne Sahaya & Emily Aguilar-Pine & Kathryn Currie & Ilya J. Finkelstein & Valerie Anda & Brett J. Baker, 2024. "Asgard archaea defense systems and their roles in the origin of eukaryotic immunity," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    2. Sam C. Went & David M. Picton & Richard D. Morgan & Andrew Nelson & Aisling Brady & Giuseppina Mariano & David T. F. Dryden & Darren L. Smith & Nicolas Wenner & Jay C. D. Hinton & Tim R. Blower, 2024. "Structure and rational engineering of the PglX methyltransferase and specificity factor for BREX phage defence," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Nathalie Béchon & Nitzan Tal & Avigail Stokar-Avihail & Alon Savidor & Meital Kupervaser & Sarah Melamed & Gil Amitai & Rotem Sorek, 2024. "Diversification of molecular pattern recognition in bacterial NLR-like proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Florian Tesson & Alexandre Hervé & Ernest Mordret & Marie Touchon & Camille d’Humières & Jean Cury & Aude Bernheim, 2022. "Systematic and quantitative view of the antiviral arsenal of prokaryotes," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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