Bat genomes illuminate adaptations to viral tolerance and disease resistance

• 成果类型: Article
• 署名作者: 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; Davalos, 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.; Banerjee, Arinjay; Irving, Aaron T.; Hiller, Michael
• 署名单位: Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Goethe University Frankfurt; University of Edinburgh; Zhejiang University; Max Planck Society; Helmholtz Association; Helmholtz-Zentrum Dresden-Rossendorf (HZDR); University of Saskatchewan; University of Saskatchewan; University College Dublin; Max Planck Society; State University of New York (SUNY) System; Stony Brook University; Tel Aviv University; Tel Aviv University; State University of New York (SUNY) System; Stony Brook University; University of St Andrews; Institut Universitaire de France; Centre National de la Recherche Scientifique (CNRS); Institut de Recherche pour le Developpement (IRD); Universite de Montpellier; University of London; Queen Mary University London; Robert Koch Institute; Texas Tech University System; Texas Tech University; Royal Ontario Museum; University of Waterloo; University of Toronto; University of British Columbia; Zhejiang University; Zhejiang University; University of Edinburgh; Smith College
• 刊物名称: Nature
• ISSN/ISSBN: 0028-1006
• DOI: 10.1038/s41586-024-08471-0
• 发表日期: 2025-02-13
• 关键词: molecular-dynamics; gene lists; rig-i; activation; virus; host; EVOLUTION; MODEL; isg15; TREE

摘要

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.