Bat genomes illuminate adaptations to viral tolerance and disease resistance
Abstract
Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order. Infections in bats are largely asymptomatic, 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.
Related
- Comparative Effects of Different Carbohydrate–Protein Formulations on Resistance Training Adaptations in Healthy Young Men
- Host-transposable element coexistence: a matter of resistance, tolerance and trade-off
- The intensity and spatial dispersion of within‐plant herbivory drive trait‐specific resistance and tolerance in wild cotton
- Gapless Complete Genome and Multi-Omics Illuminate Immune Adaptation and Host-Virus Interactions in a Coronavirus Reservoir.
- Shewanella oneidensis employs both β-lactam resistance and tolerance controlled by the PghKR system
BibTeX
@article{morales2026genomes,
title = {{Bat genomes illuminate adaptations to viral tolerance and disease resistance}},
author = {Ariadna Morales and Yue Dong and Thomas Brown and Kaushal Baid and Dimitrios Kontopoulos and Victoria Gonzalez and Zixia Huang and Alexis-Walid Ahmed and Arkadeb Bhuinya and Leon Hilgers and Sylke Winkler and Graham Hughes and Xiaomeng Li and Ping Lu and Yixin Yang and Bogdan Kirilenko and Paolo Devanna and Tanya Lama and Yomiran Nissan and Martin Pippel and Liliana Dávalos and Sonja Vernes and Sebastien Puechmaille and Stephen Rossiter and Yossi Yovel and Joseph Prescott and Andreas Kurth and David Ray and Burton Lim and Eugene Myers and Emma Teeling and Arinjay Banerjee and Aaron Irving and Michael Hiller},
journal = {Nature},
year = {2026},
month = oct,
doi = {10.1038/s41586-024-08471-0},
url = {https://hal.science/hal-04954919v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Bat genomes illuminate adaptations to viral tolerance and disease resistance
AU - Ariadna Morales
AU - Yue Dong
AU - Thomas Brown
AU - Kaushal Baid
AU - Dimitrios Kontopoulos
AU - Victoria Gonzalez
AU - Zixia Huang
AU - Alexis-Walid Ahmed
AU - Arkadeb Bhuinya
AU - Leon Hilgers
AU - Sylke Winkler
AU - Graham Hughes
AU - Xiaomeng Li
AU - Ping Lu
AU - Yixin Yang
AU - Bogdan Kirilenko
AU - Paolo Devanna
AU - Tanya Lama
AU - Yomiran Nissan
AU - Martin Pippel
AU - Liliana Dávalos
AU - Sonja Vernes
AU - Sebastien Puechmaille
AU - Stephen Rossiter
AU - Yossi Yovel
AU - Joseph Prescott
AU - Andreas Kurth
AU - David Ray
AU - Burton Lim
AU - Eugene Myers
AU - Emma Teeling
AU - Arinjay Banerjee
AU - Aaron Irving
AU - Michael Hiller
PY - 2026
DA - 2026/10/07
JO - Nature
DO - 10.1038/s41586-024-08471-0
UR - https://hal.science/hal-04954919v1
AB - Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order. Infections in bats are largely asymptomatic, 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.
SN - 0028-0836
SN - 1476-4687
ER -