Abstract：
Bats are the natural reservoir hosts of some viruses, some of which may spill over to humans and cause global-scale pandemics. Different from humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I IFNs (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments about whether bats have a contracted genome locus or constitutively expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lack of pan-bat analysis, the common characteristics of bat IFN-Is have not been revealed yet. In this study, we characterized the IFN-I locus for nine Yangochiroptera bats and three Yinpterochiroptera bats on the basis of their high-quality bat genomes. We also compared the basal expression in six bats and compared the antiviral and antiproliferative activity and the thermostability of representative Rhinolophus bat IFNs. We found a dominance of unconventional IFNω-like responses in the IFN-I system, which is unique to bats. In contrast to IFNα-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFNω-like genes (IFNω or related IFNαω), but with fewer or even no IFNα genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFNω-like gene. Likewise, the highly expressed IFNω-like protein also demonstrated the best antiviral activity, antiproliferative activity, or thermostability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique, to our knowledge, characteristics in the IFN-I system, which provide insights into our understanding of the innate immunity that contributes to a special coexistence between bats and viruses.
摘要：
蝙蝠是一些病毒的天然宿主,其中一些可能会蔓延到人类，并导致全球范围的流行病。不同于人类,蝙蝠可能与高致病性病毒共存，而不会表现出疾病的症状。作为最重要的第一防御之一，蝙蝠I型IFN（IFN-Is）被认为在这种病毒共存中起作用，因此近年来进行了研究。然而,关于蝙蝠是否具有收缩的基因组基因座或组成型表达的IFN，主要是由于特定物种的发现。我们假设由于缺乏pan-bat分析，蝙蝠IFN-Is的共同特征尚未揭示。在这项研究中,我们根据其高质量的蝙蝠基因组，对9只扬翅目蝙蝠和3只银翅目蝙蝠的IFN-I基因座进行了表征。我们还比较了六只蝙蝠的基础表达，并比较了代表性犀牛蝙蝠IFN的抗病毒和抗增殖活性以及热稳定性。我们发现IFN-I系统中非常规IFNω样反应占主导地位，这是蝙蝠独有的。与大多数其他哺乳动物中IFNα主导的IFN-I基因座相反，蝙蝠通常具有较短的IFN-I基因座，具有更多非常规的IFNω样基因（IFNω或相关的IFNαω），但有较少甚至没有IFNα基因。此外,蝙蝠通常具有组成型表达的IFN，其中表达最高的更可能是IFNω样基因。同样，高表达的IFNω样蛋白也表现出最佳的抗病毒活性，抗增殖活性，或热稳定性，如代表性的犀牛蝙蝠物种所示。总的来说,我们揭示了泛蝙蝠的独特之处，根据我们的知识，IFN-I系统的特征，这提供了我们对先天免疫的理解的见解，先天免疫有助于蝙蝠和病毒之间的特殊共存。
