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

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 M. C. Gobeil, Linfa Wang, Andrew C. Doxey and Arinjay Banerjee ()
Additional contact information
Victoria Gonzalez: University of Saskatchewan
Briallen Lobb: University of Waterloo
Jacob Côté: Faculté des Sciences et de Génie Université Laval
Arkadeb Bhuinya: University of Saskatchewan
Adriana G. Tubb: Guildford
Stephen S. Nuthalapati: Guildford
Akarin Asavajaru: University of Saskatchewan
Yan Zhou: University of Saskatchewan
Vikram Misra: University of Saskatchewan
Darryl Falzarano: University of Saskatchewan
Trevor R. Sweeney: Guildford
Sophie M. C. Gobeil: Faculté des Sciences et de Génie Université Laval
Linfa Wang: Duke-NUS Medical School
Andrew C. Doxey: University of Waterloo
Arinjay Banerjee: University of Saskatchewan

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61254-7

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