Establishment of a Bat Resource for Infectious Disease Research

建立用于传染病研究的蝙蝠资源

• 批准号: 10495114
• 负责人: Jonathan H Epstein
• 金额: $ 169.41万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10495114
• 关键词: 2019-nCoV; Address; Affect; Animal Model; Animals; Archives; Asia; Bangladesh; Biology; Bone Marrow; Breeding; Caring; Cell Culture Techniques; Cell Line; Cells; Chiroptera; Clinical; Colorado; Communities; Coronavirus; Coronavirus Infections; Dendritic Cells; Development; Disease; Disease Outbreaks; Ebola virus; Encephalitis; Event; FLT3 ligand; Family Pteropodidae; Filovirus; Flow Cytometry; Freezing; Future; Genus Pteropus; Granulocyte-Macrophage Colony-Stimulating Factor; Health; Hendra Virus; Henipavirus; Henipavirus Infections; Hepatitis C virus; Human; Immune; Immune response; Immunology; In Vitro; Individual; Infection; Infection Control; Infectious Diseases Research; Innate Immune Response; Interleukin-2; Interleukin-4; Kinetics; Knowledge; Laboratories; Macrophage; Mammals; Marburgvirus; Measles; Methodological Studies; Middle East Respiratory Syndrome Coronavirus; Modeling; Monoclonal Antibodies; Mumps; Natural Immunity; Nipah Virus; Outcome; Paramyxovirus; Pathogenicity; Pathology; Physiology; Predisposition; Primary Cell Cultures; Proteins; Proteomics; Quarantine; Reagent; Recombinant Cytokines; Recombinant Proteins; Research; Research Personnel; Resolution; Resources; Risk; SARS coronavirus; Sarbecovirus; Severe Acute Respiratory Syndrome; Study models; Surface Antigens; T-Lymphocyte; Testing; Therapeutic; Tissues; Universities; Viral; Virus; Virus Diseases; Work; Zoonoses; adaptive immune response; bat-borne; betacoronavirus; biobank; cell immortalization; coronavirus treatment; cytokine; deep sequencing; detection assay; experimental study; germ free condition; improved; in vitro testing; in vivo; metabolomics; mortality; novel; novel therapeutic intervention; offspring; pandemic potential; pathogen; pathogenic virus; prevent; trait; transcriptomics

Modified Project Summary/Abstract Section Project Summary / Abstract Bats are reservoirs, or suspected reservoirs, of many zoonotic viruses, including SARS, SARS2 and MERS coronaviruses, Nipah and Hendra viruses, and Ebola and Marburg viruses. Little is known about how these viruses circulate in their bat reservoirs, principally because of a lack of bat colonies that can be used for the development of experimental infection models. To address this deficiency, we will capture horseshoe bats and Indian flying foxes, respective reservoir hosts of Nipah virus and SARS-related coronaviruses, in Bangladesh where they will be quarantined and provided veterinary care as they adapt to captivity. Bats will be shipped to CSU to establish the breeding colonies as a resource for investigators who study these viruses. We will generate primary cell cultures and immortalized cell lines from various tissues and freeze live bone marrow that will be useful for studying how these viruses infect bat cells, and how the viruses may modulate the innate immune responses. Recombinant cytokines will also be produced for the research community, including those for generating macrophages and dendritic cells (GM-CSF, Flt3L), T cells (IL-2) and for in vivo modulation of the adaptive immune response (IFNγ, IL-4). Moreover, we will generate monoclonal antibodies for use in cytokine detection assays and flow cytometry of immune cell subsets and in vivo neutralization. Finally, we will perform experimental infection studies of Nipah virus, SARS-CoV-2 and the SARS-related coronaviruses, BANAL-52 and BANAL-236, to study the infection kinetics, virus distribution and transcriptomic, proteomic and metabolomic profiles of bats during infection, and escalation and resolution of the immune response. Tissues, cells and sera from naïve and infected bats will be archived in a biobank that will be made available to the research community. The establishment of this resource will lead to a better understanding of how bats host highly pathogenic viruses without disease and may shed light on events that increase spillover risks to humans. In turn, this information could lead to development of mitigation strategies to prevent future virus spillover and uncover new strategies for therapeutic treatment of coronavirus and Nipah virus diseases.

修改项目摘要/摘要部分 蝙蝠是许多人畜共患病毒的宿主或疑似宿主，包括SARS、SARS 2和MERS冠状病毒、尼帕病毒和亨德拉病毒、埃博拉病毒和马尔堡病毒。人们对这些病毒如何在蝙蝠宿主中传播知之甚少，主要是因为缺乏可用于开发实验感染模型的蝙蝠群体。为解决这一不足，我们将在孟加拉国捕获马蹄蝙蝠和印度狐蝠，它们分别是尼帕病毒和SARS相关冠状病毒的宿主，并将在它们适应圈养时进行隔离和提供兽医护理。蝙蝠将被运到CSU建立繁殖群，作为研究这些病毒的研究人员的资源。我们将从各种组织中产生原代细胞培养物和永生化细胞系，并冷冻活骨髓，这将有助于研究这些病毒如何感染蝙蝠细胞，以及病毒如何调节先天免疫反应。还将为研究界生产重组细胞因子，包括用于产生巨噬细胞和树突状细胞（GM-CSF，Flt 3L），T细胞（IL-2）以及用于体内调节适应性免疫应答（IFNγ，IL-4）的细胞因子。此外，我们将产生用于细胞因子检测测定和免疫细胞亚群的流式细胞术以及体内中和的单克隆抗体。最后，我们将进行尼帕病毒，SARS-CoV-2和SARS相关的冠状病毒，BANAL-52和BANAL-236的实验感染研究，研究感染动力学，病毒分布和转录组学，蛋白质组学和代谢组学的蝙蝠在感染过程中，以及免疫反应的升级和解决。来自未感染和感染蝙蝠的组织、细胞和血清将被存档在一个生物库中，供研究界使用。这一资源的建立将有助于更好地了解蝙蝠如何在没有疾病的情况下宿主高致病性病毒，并可能揭示增加人类溢出风险的事件。反过来，这些信息可能导致制定缓解策略，以防止未来的病毒溢出，并发现新的冠状病毒和尼帕病毒疾病的治疗策略。