Assessing the interferome in novel, purpose-driven bat-derived cells

评估新型目的驱动的蝙蝠源细胞的干扰素组 总结/摘要 在过去的十年里，蝙蝠已经成为一种有趣的哺乳动物， 影响导致人类和农业动物严重疾病的病毒。然而， 自然或实验感染这些病毒不会产生疾病的临床症状。因此，在本发明中， 了解蝙蝠如何耐受病毒感染可能有助于我们开发新药或发现新的 替代哺乳动物物种如人类的药物靶点。尽管最近蝙蝠的进步 免疫学，研究在很大程度上依赖于选定的蝙蝠物种的细胞培养模型，限制了我们的研究。 了解这种多样的哺乳动物秩序。翼手目由1420多个物种组成 少数蝙蝠的数据并不代表所有蝙蝠的进化适应。此外，本发明还提供了一种方法， 这些试剂在公共储存库中不可用，使得研究团体很难 追求这个有趣的和不断增长的研究领域。 对于我们的建议，我们建议开发新的蝙蝠试剂，包括初级和永生化 来自五种主要蝙蝠物种的细胞，Rousettus aegyptiacus、Pteropus alecto、Eptesicus fuscus、Artibeus jamaicensis和Aprilia perspicillata，代表目前存在于研究群体中的蝙蝠， 使得未来的体内转化研究可行且合乎逻辑。数据来自选定的蝙蝠，如 Rousettus、Pteropus和Eptesicus蝙蝠表明，蝙蝠细胞在它们的进化过程中已经进化出了适应性。 细胞因子应答，以相对于人类更好地耐受病毒感染。I型干扰素（IFN） 免疫应答是哺乳动物抗病毒防御的第一道防线，尽管I型IFN及其 下游效应已在选定的蝙蝠细胞，全球细胞反应和全方位的研究 干扰素介导的抗病毒作用或“干扰素组”仍然难以捉摸。在这个项目中，我们将使用我们的 不同的蝙蝠细胞类型，来自多个蝙蝠物种，以确定和描绘进化 保守和独特的蝙蝠特异性IFN应答。我们的研究结果将揭示有趣的 关于蝙蝠控制人畜共患RNA病毒感染的能力的问题，沿着 哺乳动物I型IFN途径进化适应的重要发现。重要的是， 我们的研究将产生关键的蝙蝠试剂，如原代细胞，细胞系，重组细胞因子， 和分子分析，这将有助于更大的合作项目的发展，研究蝙蝠 免疫学

Assessing the interferome of novel, purpose-driven bat-derived cells SUMMARY/ABSTRACT Over the last decade, bats have emerged as intriguing mammalian reservoirs of emerging high impact viruses that cause severe disease in humans and agricultural animals. However, bats that are naturally or experimentally infected with these viruses do not develop clinical signs of disease. Thus, understanding how bats tolerate virus infections may allow us to develop novel drugs or identify new drug targets for alternate mammalian species, such as humans. In spite of recent advances in bat immunology, studies have largely relied on cell culture models from selected bat species, limiting our understanding of this diverse mammalian order. The order Chiroptera is made up of over 1420 species of bats, and data from a handful of bats do not represent evolutionary adaptations in all bats. In addition, these reagents are not available on public repositories making it hard for the research community to pursue this intriguing and growing field of research. For our proposal, we propose to develop novel bat reagents, including primary and immortalized cells from five major bat species, Rousettus aegyptiacus, Pteropus alecto, Eptesicus fuscus, Artibeus jamaicensis, and Carollia perspicillata, representing bats that currently exist in research colonies, making future in vivo translational studies feasible and logical. Data from selected bats, such as Rousettus, Pteropus and Eptesicus bats suggest that bat cells have evolved adaptations in their cytokine responses to better tolerate virus infections relative to humans. Type I interferon (IFN) responses are the first line of mammalian antiviral defense, and although type I IFNs and their downstream effects have been studied in selected bat cells, global cellular responses and the full range of IFN-mediated antiviral effects or the ‘interferome’ remain elusive. For this project, we shall use our diverse bat cell types, derived from multiple bat species, to identify and delineate evolutionarily conserved and unique bat-specific IFN responses. Results from our study will shed light on intriguing questions around the ability of bats to control infection with zoonotic RNA viruses, along with making important discoveries on evolutionary adaptations in the mammalian type I IFN pathway. Importantly, our research will generate critical bat reagents, such as primary cells, cell lines, recombinant cytokines and molecular assays that will facilitate the development of larger collaborative projects to study bat immunology.