Crossing scales to predict and prevent bat virus zoonoses in a Madagascar ecosystem

跨尺度预测和预防马达加斯加生态系统中的蝙蝠病毒人畜共患病

基本信息

批准号：
10697346
负责人：
Cara Brook
金额：
$ 46.19万
依托单位：
UNIVERSITY OF CHICAGO
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：
2022-09-05 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10697346
关键词：
2019-nCoV Address African Animals Anti-Inflammatory Agents Biology COVID-19 pandemic effects Canis familiaris Case Fatality Rates Cell Line Chicago Chiroptera Circulation Clinical Collaborations Communicable Diseases Communities Consumption Coronavirus Coupled Data Discipline Disease Disparate Doctor of Philosophy Ebola Ecology Economics Ecosystem Evolution Exhibits Exposure to Filovirus Food Fruit Future Goals Hendra Virus Henipavirus Henipavirus Infections Human Immune Immune system Immunity Immunologics Infection Infection Control Innate Immune Response Intervention Island Jamaican Laboratories Learning Link Literature Madagascar Mammals Marburgvirus Measles Middle East Respiratory Syndrome Middle East Respiratory Syndrome Coronavirus Modeling Molecular Molecular Immunology Monitor Nature Nutritional Paramyxovirus Pathology Pattern Periodicals Physiologic pulse Physiological Physiology Population Population Sizes Population Study Postdoctoral Fellow Prevention Process Public Health Rabies virus Recommendation Recrudescences Regimen Research Resources Sampling Seasonal Variations Seasons Series Serology Severe Acute Respiratory Syndrome Shapes Source Stress System Techniques Testing Time United States National Institutes of Health Universities Vaccinated Vaccination Vaccines Viral Viral Load result Virulent Virus Virus Diseases Virus Shedding Work Zoonoses antiviral immunity bat-borne betacoronavirus chronic infection cost effective cross-species transmission design experience exposed human population field study immunopathology infectious disease model innovation interest mathematical model novel pandemic preparedness pathogen post-doctoral training prevent professor reproductive skills spillover event stressor therapy design tool transmission process vaccine distribution viral transmission willingness zoonotic spillover

2019-nCoV Address African Animals Anti-Inflammatory Agents Biology COVID-19 pandemic effects Canis familiaris Case Fatality Rates Cell Line Chicago Chiroptera Circulation Clinical Collaborations Communicable Diseases Communities Consumption Coronavirus Coupled Data Discipline Disease Disparate Doctor of Philosophy Ebola Ecology Economics Ecosystem Evolution Exhibits Exposure to Filovirus Food Fruit Future Goals Hendra Virus Henipavirus Henipavirus Infections Human Immune Immune system Immunity Immunologics Infection Infection Control Innate Immune Response Intervention Island Jamaican Laboratories Learning Link Literature Madagascar Mammals Marburgvirus Measles Middle East Respiratory Syndrome Middle East Respiratory Syndrome Coronavirus Modeling Molecular Molecular Immunology Monitor Nature Nutritional Paramyxovirus Pathology Pattern Periodicals Physiologic pulse Physiological Physiology Population Population Sizes Population Study Postdoctoral Fellow Prevention Process Public Health Rabies virus Recommendation Recrudescences Regimen Research Resources Sampling Seasonal Variations Seasons Series Serology Severe Acute Respiratory Syndrome Shapes Source Stress System Techniques Testing Time United States National Institutes of Health Universities Vaccinated Vaccination Vaccines Viral Viral Load result Virulent Virus Virus Diseases Virus Shedding Work Zoonoses antiviral immunity bat-borne betacoronavirus chronic infection cost effective cross-species transmission design experience exposed human population field study immunopathology infectious disease model innovation interest mathematical model novel pandemic preparedness pathogen post-doctoral training prevent professor reproductive skills spillover event stressor therapy design tool transmission process vaccine distribution viral transmission willingness zoonotic spillover

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项目摘要

The wide-reaching impacts of the COVID-19 pandemic highlight the extreme threat posed by the cross-species emergence of zoonotic pathogens. Bats (order: Chiroptera) are the natural reservoir hosts for the majority of the world’s most virulent zoonotic viruses, including Hendra and Nipah henipaviruses, Ebola and Marburg filoviruses, and SARS, MERS, and now SARS-CoV-2 coronaviruses. Remarkably, bats exhibit little demonstrable disease upon infection with viruses that cause extreme pathology in other mammals, likely in part due to their unique anti-inflammatory molecular adaptations, which are thought to have evolved to mitigate the accumulation of physiological damage accrued during flight. Surprisingly, isolated island bat communities around the world support the endemic circulation of numerous viruses in populations below the critical community size required for persistence of related pathogens in other hosts. Since cross-species spillover of several bat-borne viruses bears a distinctive seasonal signature, coincident with the timing of reproductive and nutritional stress for the bat hosts in question, disentangling the mechanisms governing the transmission, circulation, and persistence of these viruses in wild bat populations is of critical public health interest. In part with the research initiatives proposed here, we will use molecular and serological tools to develop a longitudinal time series of immunological and infection data for henipaviruses and coronaviruses circulating in wild fruit bats in Madagascar, leveraging samples collected in our longterm wildlife surveillance effort. Bats are widely consumed as a source of human food in Madagascar, and preliminary data from our research group demonstrates serological signatures of prior human exposure to these zoonotic viruses across the island. We propose to fit disparate dynamical models to the resulting population-level data in order to distinguish mechanisms underpinning seasonal viral shedding pulses and concomitant transmission in these bat hosts. In addition to population-level studies, we will also construct within-host models of viral control in a single bat immune system, which we will fit to experimental infection data from Betacoronavirus-challenged bats in the laboratory, with the aim of deciphering the mechanisms which motivate viral shedding. Our project aims to simultaneously develop molecular tools of bat cell lines and viruses with which to support within-host studies in our own Madagascar system. Finally, we will build on population-level and within-host studies to model and implement a vaccine intervention designed to eradicate circulating henipavirus from a test-population of Madagascar fruit bats. Broadly, our project aims to use a uniquely integrative combination of field, molecular, and modeling tools to enable the prediction and prevention of bat virus spillover events before they occur.

共证19大流行的广泛影响突出了跨物种构成的极端威胁人畜共患病原体的出现。蝙蝠（命令：脊骨翅目）是大多数的天然储层宿主世界上最有毒的人畜共患病毒，包括Hendra和Nipah Henipaviruses，Ebola和Marburg 丝状病毒，SARS，MERS和现在的SARS-COV-2冠状病毒。值得注意的是，蝙蝠很少在感染其他哺乳动物中引起极端病理的病毒后，可证明的疾病，可能部分是由于它们独特的抗炎分子适应性，被认为是为了减轻而发展的飞行过程中受到的身体损害的积累。令人惊讶的是，孤立的岛屿蝙蝠社区世界各地支持关键以下种群中众多病毒的地方性圈子其他宿主中相关病原体持续性所需的社区大小。由于跨物种的Spilover 几种蝙蝠传播的病毒带有独特的季节性签名，与繁殖时机和蝙蝠宿主的营养应力，解散了传输的机制，野生蝙蝠种群中这些病毒的流通和持久性是至关重要的公共卫生利益。部分根据这里提出的研究计划，我们将使用分子和血清学工具来开发 Henipaviruses和冠状病毒的免疫学和感染数据的纵向时间序列马达加斯加的野生蝙蝠，利用我们的长期野生动植物监视工作中收集的样品。蝙蝠是广泛作为马达加斯加人类食品的来源以及我们研究小组的初步数据证明了岛上人类动物病毒事先接触这些人畜共患病的血清学特征。我们将不同的动态模型拟合到由此产生的人群级数据的建议，以区分这些蝙蝠宿主的季节性病毒脱落和伴随的传播的机制。在除了人口级研究外，我们还将在单个BAT中构建病毒控制的主机内模型免疫系统，我们将适合来自Betacoronavirus挑战蝙蝠的实验感染数据实验室，目的是破译动机病毒脱落的机制。我们的项目旨在类似地开发了蝙蝠细胞系和病毒的分子工具，以支持宿主内部研究我们自己的马达加斯加系统。最后，我们将以人口级和宿主内研究为基础，以建模和实施旨在从循环的HENIPAVIRUS的疫苗干预措施中马达加斯加水果蝙蝠。从广义上讲，我们的项目旨在使用分子，分子，分子的唯一集成组合以及建模工具，以便在发生之前预测和预防蝙蝠病毒旋转事件。