Bat Genomes Illuminate Adaptations to Viral Tolerance and Disease Resistance

Authors

• Ariadna E. Morales, LOEWE Centre for Translational Biodiversity Genomics
• Yue Dong, Edinburgh Medical School
• Thomas Brown, Max Planck Institute of Molecular Cell Biology and Genetics
• Kaushal Baid, Vaccine and Infectious Disease Organization - International Vaccine Centre
• Dimitrios Georgios Kontopoulos, LOEWE Centre for Translational Biodiversity Genomics
• Victoria Gonzalez, Vaccine and Infectious Disease Organization - International Vaccine Centre
• Zixia Huang, University College Dublin
• Alexis Walid Ahmed, LOEWE Centre for Translational Biodiversity Genomics
• Arkadeb Bhuinya, Vaccine and Infectious Disease Organization - International Vaccine Centre
• 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, Edinburgh Medical School
• Ping Lu, Zhejiang University-University of Edinburgh Institute
• Yixin Yang, Zhejiang University-University of Edinburgh Institute
• Bogdan M. Kirilenko, LOEWE Centre for Translational Biodiversity Genomics
• Paolo Devanna, Max Planck Institute for Psycholinguistics
• Tanya M. Lama, Stony Brook UniversityFollow
• Yomiran Nissan, Tel Aviv University
• Martin Pippel, Max Planck Institute of Molecular Cell Biology and Genetics
• Liliana M. Dávalos, Stony Brook University
• 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, Vaccine and Infectious Disease Organization - International Vaccine Centre

Document Type

Article

Publication Date

1-1-2025

Publication Title

Nature

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.

DOI

10.1038/s41586-024-08471-0

ISSN

00280836

Version

Author's Accepted Manuscript

Recommended Citation

Morales, Ariadna E.; Dong, Yue; Brown, Thomas; Baid, Kaushal; Kontopoulos, Dimitrios Georgios; Gonzalez, Victoria; Huang, Zixia; Ahmed, Alexis Walid; Bhuinya, Arkadeb; Hilgers, Leon; Winkler, Sylke; Hughes, Graham; Li, Xiaomeng; Lu, Ping; Yang, Yixin; Kirilenko, Bogdan M.; Devanna, Paolo; Lama, Tanya M.; Nissan, Yomiran; Pippel, Martin; Dávalos, Liliana M.; Vernes, Sonja C.; Puechmaille, Sebastien J.; Rossiter, Stephen J.; Yovel, Yossi; Prescott, Joseph B.; Kurth, Andreas; Ray, David A.; Lim, Burton K.; Myers, Eugene; Teeling, Emma C.; and Banerjee, Arinjay, "Bat Genomes Illuminate Adaptations to Viral Tolerance and Disease Resistance" (2025). Biological Sciences: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/bio_facpubs/314