Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced viral tolerance

Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced viral tolerance | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced viral tolerance Arinjay Banerjee, Victoria Gonzalez, Briallen Lobb, Jacob Cote, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5411236/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Bats are reservoirs of emerging zoonotic viruses of concern that cause severe disease in humans and agricultural animals. However, it is poorly understood how bats are able to tolerate diverse viral infections, knowledge that could help pave the way for new therapeutic strategies. Here, we characterized antiviral pathways in two divergent bat species, Pteropus alecto and Eptesicus fuscus, identifying unique bat-specific mechanisms underlying their enhanced antiviral tolerance. We demonstrate the critical roles of STAT1 and STAT2 in IFNβ signaling, along with species-specific adaptations that collectively contribute towards a “steady and ready” antiviral state in bat cells. Unlike in humans, we find that bat interferon signalling processes resist the immune antagonistic properties of viruses like MERS-CoV which further explains the ability of bats to tolerate coronavirus infections. Using transcriptomic analysis, we identified canonical and non-canonical interferon stimulated genes (ISGs) including two key bat genes, IFIT1 and GBP1. Compared to their human orthologs, we show that bat IFIT1 and GBP1 exhibit enhanced antiviral activity against a wide range of RNA and DNA viruses, including coronaviruses and additional bat-derived poxviruses (e.g., Eptesipoxvirus). Ultimately, our work provides important insights into the evolution of enhanced interferon-mediated antiviral responses in bats, contributing to their unique ability to resist viral diseases. Biological sciences/Microbiology/Virology/Virus–host interactions Biological sciences/Microbiology/Virology/Viral reservoirs Full Text Additional Declarations Yes there is potential Competing Interest. A.B. is a co-inventor of the Efk3B cell line that is sold through Kerafast, USA. All authors declare no other conflicts of interest. Supplementary Files SupplementaryTablesS1S7.xlsx Supplementary Tables S1-S7 SupplementalMaterials.pdf Supplementary Figures 1-17 Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5411236","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":382380623,"identity":"2a00dc54-1377-48c0-8fe8-90c597a02132","order_by":0,"name":"Arinjay 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However, it is poorly understood how bats are able to tolerate diverse viral infections, knowledge that could help pave the way for new therapeutic strategies. Here, we characterized antiviral pathways in two divergent bat species, Pteropus alecto and Eptesicus fuscus, identifying unique bat-specific mechanisms underlying their enhanced antiviral tolerance. We demonstrate the critical roles of STAT1 and STAT2 in IFNβ signaling, along with species-specific adaptations that collectively contribute towards a “steady and ready” antiviral state in bat cells. Unlike in humans, we find that bat interferon signalling processes resist the immune antagonistic properties of viruses like MERS-CoV which further explains the ability of bats to tolerate coronavirus infections. Using transcriptomic analysis, we identified canonical and non-canonical interferon stimulated genes (ISGs) including two key bat genes, IFIT1 and GBP1. Compared to their human orthologs, we show that bat IFIT1 and GBP1 exhibit enhanced antiviral activity against a wide range of RNA and DNA viruses, including coronaviruses and additional bat-derived poxviruses (e.g., Eptesipoxvirus). 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