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

评估新型、目的驱动的蝙蝠来源细胞中的干扰素

基本信息

批准号：
10451405
负责人：
Arinjay Banerjee
金额：
$ 17.02万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-09 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10451405
关键词：
2019-nCoV Agriculture Animals Biological Assay Brain Cell Culture Techniques Cell Line Cells Chiroptera Clinical Clone Cells Collection Communities Comparative Study Competence Complement Receptor Coronavirus Critical Pathways Data Development Disease Feasibility Studies Future Genus Pteropus Goals Human Immunologics Immunology Infection Infection Control Innate Immune Response Interferon Type I Interferons Kidney Knowledge Laboratories Light Liver Lung Mediating Middle East Respiratory Syndrome Coronavirus Modeling Molecular Natural Immunity Nipah Virus Pathway interactions Poly I-C Predisposition Primary Cell Cultures Process RNA Viruses Reagent Recombinant Cytokines Recombinants Reporter Research Research Personnel Resistance Rousettus SARS coronavirus Sendai virus Spleen Testing Therapeutic Tissues Tropism Vesicular stomatitis Indiana virus Viral Virus Virus Diseases Virus Receptors Virus Replication Zoonoses antiviral immunity base bat-borne betacoronavirus cell culture collection cell immortalization cell type cytokine experience global health in vitro Model in vivo innate immune pathways new therapeutic target novel novel therapeutics particle pathogen pathogenic virus public repository response tool translational study

项目摘要

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.

评估新型、目的驱动的蝙蝠来源细胞的干扰素摘要/摘要在过去的十年中，蝙蝠已成为新兴高风险哺乳动物的有趣储存库。影响导致人类和农业动物严重疾病的病毒。自然或实验感染这些病毒不会出现疾病的临床症状。了解蝙蝠如何耐受病毒感染可能使我们能够开发新药物或识别新药物尽管最近在蝙蝠方面取得了进展，但针对其他哺乳动物物种（例如人类）的药物靶标。免疫学方面，研究很大程度上依赖于选定蝙蝠物种的细胞培养模型，限制了我们的研究翼手目由 1420 多个物种组成。蝙蝠的数量，来自少数蝙蝠的数据并不代表所有蝙蝠的进化适应。这些试剂在公共存储库中不可用，这使得研究界很难追求这个有趣且不断发展的研究领域。对于我们的建议，我们建议开发新型蝙蝠试剂，包括初级和永生化试剂来自五种主要蝙蝠物种（Rousettus aegyptiacus、Pteropus alecto、Eptesicus fuscus、Artibeus）的细胞 jamaicensis 和 Carollia perspicillata 代表目前存在于研究群体中的蝙蝠，使未来的体内转化研究成为可能且合乎逻辑的来自选定蝙蝠的数据。 Rousettus、Pteropus 和 Eptesicus 蝙蝠表明，蝙蝠细胞已经进化出适应性相对于人类，细胞因子反应可以更好地耐受病毒感染。反应是哺乳动物抗病毒防御的第一道防线，尽管 I 型干扰素及其下游效应已在选定的蝙蝠细胞、整体细胞反应和全方位中进行了研究干扰素介导的抗病毒作用或“干扰组”仍然难以捉摸，对于这个项目，我们将使用我们的。来自多种蝙蝠物种的不同蝙蝠细胞类型，用于识别和描绘进化过程我们的研究结果将揭示出保守且独特的蝙蝠特异性干扰素反应。关于蝙蝠控制人畜共患 RNA 病毒感染的能力的问题，以及关于哺乳动物 I 型干扰素途径进化适应的重要发现。我们的研究将产生关键的蝙蝠试剂，例如原代细胞、细胞系、重组细胞因子和分子检测将有助于开发更大的蝙蝠研究合作项目免疫学。