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; Michael Hiller

doi:10.1038/s41586-024-08471-0

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 PippelLiliana 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^*, Michael Hiller^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 asymptomatic^2,3, 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.

Original language	English
Pages (from-to)	449-458
Number of pages	10
Journal	Nature
Volume	638
Issue number	8050
Early online date	29 Jan 2025
DOIs	https://doi.org/10.1038/s41586-024-08471-0
Publication status	Published - 13 Feb 2025

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1 Finished
1 Active

BATSPEAK: BATSPEAK
Vernes, S. (PI)
European Research Council
1/05/22 → 30/04/27
Project: Standard
Sonja Vernes UKRI Future Leaders: Mammalian vocal communication as a model for human language; from genes and brains to behaviour
Vernes, S. (PI)
UK Research and Innovation
1/11/20 → 31/10/25
Project: Fellowship

Bat genomes illuminate adaptations to viral tolerance and disease resistance (dataset)
Vernes, S. (Creator), NCBI GenBank, 2026
https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA949177 and 9 more links, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA938463, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA938461, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA938462, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA955779, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA938455, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA939732, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA971926, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA940731, https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA949178 (show fewer)
Dataset

Cite this

Morales, A. E., Dong, Y., Brown, T., Baid, K., Kontopoulos, D. . G., Gonzalez, V., Huang, Z., Ahmed, A. W., Bhuinya, A., Hilgers, L., Winkler, S., Hughes, G., Li, X., Lu, P., Yang, Y., Kirilenko, B. M., Devanna, P., Lama, T. M., Nissan, Y., ... Hiller, M. (2025). Bat genomes illuminate adaptations to viral tolerance and disease resistance. Nature, 638(8050), 449-458. https://doi.org/10.1038/s41586-024-08471-0

@article{a9995a4dcb304686a67496a58cd4f65b,

title = "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 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.",

author = "Morales, \{Ariadna E.\} and Yue Dong and Thomas Brown and Kaushal Baid and Kontopoulos, \{Dimitrios - Georgios\} and Victoria Gonzalez and Zixia Huang and Ahmed, \{Alexis Walid\} and Arkadeb Bhuinya and Leon Hilgers and Sylke Winkler and Graham Hughes and Xiaomeng Li and Ping Lu and Yixin Yang and Kirilenko, \{Bogdan M.\} and Paolo Devanna and Lama, \{Tanya M.\} and Yomiran Nissan and Martin Pippel and D{\'a}valos, \{Liliana M.\} and Vernes, \{Sonja C.\} and Puechmaille, \{Sebastien J.\} and Rossiter, \{Stephen J.\} and Yossi Yovel and Prescott, \{Joseph B.\} and Andreas Kurth and Ray, \{David A.\} and Lim, \{Burton K.\} and Eugene Myers and Teeling, \{Emma C.\} and Arinjay Banerjee and Irving, \{Aaron T.\} and Michael Hiller",

note = "Funding: M.H. was supported by the German Research Foundation (HI1423/5-1) and the LOEWE-Centre for Translational Biodiversity Genomics, funded by the Hessen State Ministry of Higher Education, Research and the Arts (LOEWE/1/10/519/03/03.001(0014)/52); T.B. by the German Research Foundation (INST 269/768-1); L.M.D. by the National Science Foundation (NSF-IOS 2032063 and 2031906, and NSF-DEB 1838273); T.M.L. by the National Science Foundation (award ID 2010853); A.T.I. by a Key grant from the National Science Foundation of Zhejiang Province (Z23C010001) and a National Science Foundation Research Fund for International Excellent Young Scientists (RFIS-II, 82350610279); B.K.L. by the Royal Ontario Museum Governors, the National Science Foundation (DEB-0344430) and the Toronto Zoological Society; A. Banerjee by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2022-03010) and the Canadian Institutes of Health Research (CIHR) Center for Research on Pandemic Preparedness and Health Emergencies, Early Career Investigator grant (PEE-183995) and CIHR Infection and Immunity, Early Career Research Support (PTT-192089); V.G. by a PGS-D scholarship funded by the Natural Sciences and Engineering Research Council of Canada (569587-2022); S.C.V. by a UKRI Future Leaders fellowship (MR/T021985/1), an ERC Consolidator grant (101001702; BATSPEAK) and a Max Planck Research Group award from the Max Planck Society; S.J.P. by a Junior Chair grant from the Institut Universitaire de France; E.M. by the Max Planck Society; A.K. and J.B.P. by the Robert Koch Institute; E.C.T. by Irish Research Council Laureate Award IRCLA/2017/58 and Science Foundation Ireland Future Frontiers 19/FFP/6790; D. - G.K. by an EMBO postdoctoral fellowship (ALTF 1089-2021). The Vaccine and Infectious Disease Organization receives operational funding from the government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture, and funding for its Containment Level 3 facility (InterVac) from the Canada Foundation for Innovation through the Major Science Initiatives. We thank the Long Read Team of the DRESDEN-concept Genome Center, the DFG NGS Competence Center, which is part of the Center for Molecular and Cellular Bioengineering, Technische Universit{\"a}t Dresden, and of the MPI-CBG. We also thank the core facility of the Zhejiang University–University of Edinburgh Institute.",

year = "2025",

month = feb,

day = "13",

doi = "10.1038/s41586-024-08471-0",

language = "English",

volume = "638",

pages = "449--458",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "8050",

}

Morales, AE, Dong, Y, Brown, T, Baid, K, Kontopoulos, DG, Gonzalez, V, Huang, Z, Ahmed, AW, Bhuinya, A, Hilgers, L, Winkler, S, Hughes, G, Li, X, Lu, P, Yang, Y, Kirilenko, BM, Devanna, P, Lama, TM, Nissan, Y, Pippel, M, Dávalos, LM, Vernes, SC, Puechmaille, SJ, Rossiter, SJ, Yovel, Y, Prescott, JB, Kurth, A, Ray, DA, Lim, BK, Myers, E, Teeling, EC, Banerjee, A, Irving, AT & Hiller, M 2025, 'Bat genomes illuminate adaptations to viral tolerance and disease resistance', Nature, vol. 638, no. 8050, pp. 449-458. https://doi.org/10.1038/s41586-024-08471-0

TY - JOUR

T1 - Bat genomes illuminate adaptations to viral tolerance and disease resistance

AU - Morales, Ariadna E.

AU - Dong, Yue

AU - Brown, Thomas

AU - Baid, Kaushal

AU - Kontopoulos, Dimitrios - Georgios

AU - Gonzalez, Victoria

AU - Huang, Zixia

AU - Ahmed, Alexis Walid

AU - Bhuinya, Arkadeb

AU - Hilgers, Leon

AU - Winkler, Sylke

AU - Hughes, Graham

AU - Li, Xiaomeng

AU - Lu, Ping

AU - Yang, Yixin

AU - Kirilenko, Bogdan M.

AU - Devanna, Paolo

AU - Lama, Tanya M.

AU - Nissan, Yomiran

AU - Pippel, Martin

AU - Dávalos, Liliana M.

AU - Vernes, Sonja C.

AU - Puechmaille, Sebastien J.

AU - Rossiter, Stephen J.

AU - Yovel, Yossi

AU - Prescott, Joseph B.

AU - Kurth, Andreas

AU - Ray, David A.

AU - Lim, Burton K.

AU - Myers, Eugene

AU - Teeling, Emma C.

AU - Banerjee, Arinjay

AU - Irving, Aaron T.

AU - Hiller, Michael

N1 - Funding: M.H. was supported by the German Research Foundation (HI1423/5-1) and the LOEWE-Centre for Translational Biodiversity Genomics, funded by the Hessen State Ministry of Higher Education, Research and the Arts (LOEWE/1/10/519/03/03.001(0014)/52); T.B. by the German Research Foundation (INST 269/768-1); L.M.D. by the National Science Foundation (NSF-IOS 2032063 and 2031906, and NSF-DEB 1838273); T.M.L. by the National Science Foundation (award ID 2010853); A.T.I. by a Key grant from the National Science Foundation of Zhejiang Province (Z23C010001) and a National Science Foundation Research Fund for International Excellent Young Scientists (RFIS-II, 82350610279); B.K.L. by the Royal Ontario Museum Governors, the National Science Foundation (DEB-0344430) and the Toronto Zoological Society; A. Banerjee by the Natural Sciences and Engineering Research Council of Canada (RGPIN-2022-03010) and the Canadian Institutes of Health Research (CIHR) Center for Research on Pandemic Preparedness and Health Emergencies, Early Career Investigator grant (PEE-183995) and CIHR Infection and Immunity, Early Career Research Support (PTT-192089); V.G. by a PGS-D scholarship funded by the Natural Sciences and Engineering Research Council of Canada (569587-2022); S.C.V. by a UKRI Future Leaders fellowship (MR/T021985/1), an ERC Consolidator grant (101001702; BATSPEAK) and a Max Planck Research Group award from the Max Planck Society; S.J.P. by a Junior Chair grant from the Institut Universitaire de France; E.M. by the Max Planck Society; A.K. and J.B.P. by the Robert Koch Institute; E.C.T. by Irish Research Council Laureate Award IRCLA/2017/58 and Science Foundation Ireland Future Frontiers 19/FFP/6790; D. - G.K. by an EMBO postdoctoral fellowship (ALTF 1089-2021). The Vaccine and Infectious Disease Organization receives operational funding from the government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture, and funding for its Containment Level 3 facility (InterVac) from the Canada Foundation for Innovation through the Major Science Initiatives. We thank the Long Read Team of the DRESDEN-concept Genome Center, the DFG NGS Competence Center, which is part of the Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, and of the MPI-CBG. We also thank the core facility of the Zhejiang University–University of Edinburgh Institute.

PY - 2025/2/13

Y1 - 2025/2/13

N2 - 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.

AB - 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.

U2 - 10.1038/s41586-024-08471-0

DO - 10.1038/s41586-024-08471-0

M3 - Article

C2 - 39880942

AN - SCOPUS:85217160434

SN - 0028-0836

VL - 638

SP - 449

EP - 458

JO - Nature

JF - Nature

IS - 8050

ER -

Bat genomes illuminate adaptations to viral tolerance and disease resistance

Abstract

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BATSPEAK: BATSPEAK

Sonja Vernes UKRI Future Leaders: Mammalian vocal communication as a model for human language; from genes and brains to behaviour

Datasets

Bat genomes illuminate adaptations to viral tolerance and disease resistance (dataset)

Cite this