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Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced antiviral capacity

Author

Listed:
  • Victoria Gonzalez

    (University of Saskatchewan
    University of Saskatchewan)

  • Briallen Lobb

    (University of Waterloo)

  • Jacob Côté

    (Faculté des Sciences et de Génie Université Laval
    Université Laval
    Université Laval
    Université Laval)

  • Arkadeb Bhuinya

    (University of Saskatchewan
    University of Saskatchewan)

  • Adriana G. Tubb

    (Guildford)

  • Stephen S. Nuthalapati

    (Guildford)

  • Akarin Asavajaru

    (University of Saskatchewan)

  • Yan Zhou

    (University of Saskatchewan
    University of Saskatchewan)

  • Vikram Misra

    (University of Saskatchewan)

  • Darryl Falzarano

    (University of Saskatchewan
    University of Saskatchewan)

  • Trevor R. Sweeney

    (Guildford
    University of Cambridge)

  • Sophie M. C. Gobeil

    (Faculté des Sciences et de Génie Université Laval
    Université Laval
    Université Laval
    Université Laval)

  • Linfa Wang

    (Duke-NUS Medical School)

  • Andrew C. Doxey

    (University of Waterloo)

  • Arinjay Banerjee

    (University of Saskatchewan
    University of Saskatchewan
    University of Waterloo
    University of Toronto)

Abstract

Bats are reservoirs of emerging zoonotic viruses that may cause severe disease in humans and agricultural animals. However, it is poorly understood how bats can tolerate diverse viral infections. Here, we characterized type I interferon response pathways in kidney cell lines derived from two divergent bat species, Pteropus alecto and Eptesicus fuscus, identifying distinct mechanisms underlying their enhanced control of viral infection. We demonstrate the critical roles of STAT1/STAT2 in IFNβ signaling, along with species-specific adaptations that contribute towards a steady and ready antiviral state. Unlike in humans, bat IFNβ signaling processes resist the immune antagonistic properties of MERS-CoV which further explains the ability of bats to tolerate coronavirus infections. Transcriptomic analysis on interferon stimulated cell lines identified canonical and non-canonical interferon stimulated genes including two differentially expressed genes, IFIT1 and GBP1, that exhibit enhanced antiviral activity against a wide range of viruses, including the bat-derived Eptesipoxvirus. We have identified a functional (AV1) motif within E. fuscus GBP1 that restricts Eptesipoxvirus replication. Ultimately, our work provides important insights into the evolution of enhanced interferon-mediated antiviral responses in bats, contributing to their ability to resist viral diseases.

Suggested Citation

  • Victoria Gonzalez & Briallen Lobb & Jacob Côté & Arkadeb Bhuinya & Adriana G. Tubb & Stephen S. Nuthalapati & Akarin Asavajaru & Yan Zhou & Vikram Misra & Darryl Falzarano & Trevor R. Sweeney & Sophie, 2025. "Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced antiviral capacity," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61254-7
    DOI: 10.1038/s41467-025-61254-7
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    References listed on IDEAS

    as
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    3. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Addendum: Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 636(8042), pages 4-4, December.
    4. Agnidipta Ghosh & Gerrit J. K. Praefcke & Louis Renault & Alfred Wittinghofer & Christian Herrmann, 2006. "How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP," Nature, Nature, vol. 440(7080), pages 101-104, March.
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