College of Life Sciences, Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Wuhan University, Wuhan 430072, China.
Novogene Bioinformatics Institute, Beijing 100015, China.
Sci Adv. 2023 May 5;9(18):eadd0141. doi: 10.1126/sciadv.add0141.
Bats have been identified as natural reservoir hosts of several zoonotic viruses, prompting suggestions that they have unique immunological adaptations. Among bats, Old World fruit bats (Pteropodidae) have been linked to multiple spillovers. To test for lineage-specific molecular adaptations in these bats, we developed a new assembly pipeline to generate a reference-quality genome of the fruit bat and used this in comparative analyses of 12 bat species, including six pteropodids. Our results reveal that immunity-related genes have higher evolutionary rates in pteropodids than in other bats. Several lineage-specific genetic changes were shared across pteropodids, including the loss of , duplications of and , and amino acid replacements in . We introduced transgenes containing Pteropodidae-specific residues into bat and human cell lines and found evidence of dampened inflammatory responses. By uncovering distinct immune adaptations, our results could help explain why pteropodids are frequently identified as viral hosts.
蝙蝠已被确定为多种人畜共患病毒的天然宿主，这促使人们提出它们具有独特的免疫适应性的观点。在蝙蝠中，旧世界果蝠（Pteropodidae）与多种溢出事件有关。为了检测这些蝙蝠中特定谱系的分子适应性，我们开发了一种新的组装管道，以生成水果蝙蝠的参考质量基因组，并将其用于包括六种果蝠在内的 12 种蝙蝠物种的比较分析。我们的结果表明，免疫相关基因在果蝠中的进化速度高于其他蝙蝠。几个谱系特异性的遗传变化在果蝠中是共享的，包括 的缺失、 和 的重复以及 的氨基酸替换。我们将含有果蝠特异性残基的 转基因引入蝙蝠和人类细胞系，并发现了炎症反应减弱的证据。通过揭示独特的免疫适应性，我们的结果可以帮助解释为什么果蝠经常被确定为病毒宿主。
