Bat genomes illuminate adaptations to viral tolerance and disease resistance

Ariadna E. Morales, Yue Dong, Thomas Brown, Kaushal Baid, Dimitrios - Georgios Kontopoulos, Victoria Gonzalez, Zixia Huang, Alexis-Walid Ahmed, Arkadeb Bhuinya, Leon Hilgers, Sylke Winkler, Graham Hughes, Xiaomeng Li, Ping Lu, Yixin Yang, Bogdan M. Kirilenko, Paolo Devanna, Tanya M. Lama, Yomiran Nissan, Martin Pippel, Liliana M. Dávalos, Sonja C. Vernes, Sebastien J. Puechmaille, Stephen J. Rossiter, Yossi Yovel, Joseph B. Prescott, Andreas Kurth, David A. Ray, Burton K. Lim, Eugene Myers, Emma C. Teeling, Arinjay Banerjee, Aaron T. Irving () and Michael Hiller ()
Additional contact information
Ariadna E. Morales: LOEWE Centre for Translational Biodiversity Genomics
Yue Dong: The University of Edinburgh
Thomas Brown: Max Planck Institute of Molecular Cell Biology and Genetics
Kaushal Baid: University of Saskatchewan
Dimitrios - Georgios Kontopoulos: LOEWE Centre for Translational Biodiversity Genomics
Victoria Gonzalez: University of Saskatchewan
Zixia Huang: University College Dublin
Alexis-Walid Ahmed: LOEWE Centre for Translational Biodiversity Genomics
Arkadeb Bhuinya: University of Saskatchewan
Leon Hilgers: LOEWE Centre for Translational Biodiversity Genomics
Sylke Winkler: Max Planck Institute of Molecular Cell Biology and Genetics
Graham Hughes: University College Dublin
Xiaomeng Li: The University of Edinburgh
Ping Lu: Zhejiang University
Yixin Yang: Zhejiang University
Bogdan M. Kirilenko: LOEWE Centre for Translational Biodiversity Genomics
Paolo Devanna: Max Planck Institute for Psycholinguistics
Tanya M. Lama: SUNY Stony Brook
Yomiran Nissan: Tel Aviv University
Martin Pippel: Max Planck Institute of Molecular Cell Biology and Genetics
Liliana M. Dávalos: SUNY Stony Brook
Sonja C. Vernes: Max Planck Institute for Psycholinguistics
Sebastien J. Puechmaille: Institut Universitaire de France
Stephen J. Rossiter: Queen Mary University of London
Yossi Yovel: Tel Aviv University
Joseph B. Prescott: Robert Koch Institute
Andreas Kurth: Robert Koch Institute
David A. Ray: Texas Tech University
Burton K. Lim: Royal Ontario Museum
Eugene Myers: Max Planck Institute of Molecular Cell Biology and Genetics
Emma C. Teeling: University College Dublin
Arinjay Banerjee: University of Saskatchewan
Aaron T. Irving: Zhejiang University School of Medicine
Michael Hiller: LOEWE Centre for Translational Biodiversity Genomics

Nature, 2025, vol. 638, issue 8050, 449-458

Abstract: Abstract Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order1. Infections in bats are largely asymptomatic2,3, indicating limited tissue-damaging inflammation and immunopathology. To investigate the genomic basis of disease resistance, the Bat1K project generated reference-quality genomes of ten bat species, including potential viral reservoirs. Here we describe a systematic analysis covering 115 mammalian genomes that revealed that signatures of selection in immune genes are more prevalent in bats than in other mammalian orders. We found an excess of immune gene adaptations in the ancestral chiropteran branch and in many descending bat lineages, highlighting viral entry and detection factors, and regulators of antiviral and inflammatory responses. ISG15, which is an antiviral gene contributing to hyperinflammation during COVID-19 (refs. 4,5), exhibits key residue changes in rhinolophid and hipposiderid bats. Cellular infection experiments show species-specific antiviral differences and an essential role of protein conjugation in antiviral function of bat ISG15, separate from its role in secretion and inflammation in humans. Furthermore, in contrast to humans, ISG15 in most rhinolophid and hipposiderid bats has strong anti-SARS-CoV-2 activity. Our work reveals molecular mechanisms that contribute to viral tolerance and disease resistance in bats.

Date: 2025
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DOI: 10.1038/s41586-024-08471-0

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