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

评估新的、目的驱动的BAT来源细胞的干扰组 摘要/摘要 在过去的十年里，蝙蝠已经成为耐人寻味的哺乳动物新高的蓄水池。 影响在人类和农业动物中引起严重疾病的病毒。然而，蝙蝠是 自然感染或实验感染这些病毒不会出现疾病的临床症状。因此， 了解蝙蝠如何耐受病毒感染可能会让我们开发新药或识别新的 替代哺乳动物物种的药物靶标，如人类。尽管BAT最近取得了一些进展 免疫学方面，研究在很大程度上依赖于选定蝙蝠物种的细胞培养模型，限制了我们的 对这种多样化的哺乳动物目的理解。翼手目由1420多个物种组成 来自少数蝙蝠的数据并不能代表所有蝙蝠的进化适应。此外, 这些试剂在公共资料库中不可用，这使得研究界很难 继续从事这一耐人寻味且不断增长的研究领域。 在我们的建议中，我们建议开发新型BAT试剂，包括初级试剂和永生化试剂 五种蝙蝠的细胞：埃及斑潜蝇、翼手蝙蝠、青斑蝙蝠、白腹蝙蝠 Jamaicens和Carollia perspicillata，代表目前存在于研究群体中的蝙蝠， 使未来的体内翻译研究变得可行和合乎逻辑。来自选定蝙蝠的数据，例如 Rousettus、Pteropus和Eptesicus蝙蝠认为蝙蝠细胞在其 与人类相比，细胞因子反应能更好地耐受病毒感染。I型干扰素 反应是哺乳动物抗病毒防御的第一道防线，尽管I型IFN和它们的 下游效应已经在选定的蝙蝠细胞、全球细胞反应和全范围内进行了研究 关于干扰素介导的抗病毒作用或“干扰素”仍然难以捉摸。对于这个项目，我们将使用我们的 不同的蝙蝠细胞类型，来自多种蝙蝠物种，以识别和描绘进化 保守且独特的蝙蝠特异性干扰素反应。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，以及 哺乳动物I型干扰素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BAT试剂，如原代细胞、细胞系、重组细胞因子 以及分子分析，这将促进研究BAT的更大合作项目的发展 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.