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

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.

COVID-19 大流行的广泛影响凸显了跨物种构成的极端威胁人畜共患病原体的出现（蝙蝠目：翼手目）是大多数病原体的天然储存宿主。世界上毒性最强的人畜共患病毒，包括亨德拉病毒和尼帕亨尼帕病毒、埃博拉病毒和马尔堡病毒值得注意的是，蝙蝠几乎没有表现出丝状病毒、SARS、MERS 和现在的 SARS-CoV-2 冠状病毒。在感染导致其他哺乳动物极端病理的病毒后出现明显的疾病，可能在部分原因在于它们独特的抗炎分子适应，人们认为这些适应已经进化到减轻令人惊讶的是，孤立的岛屿蝙蝠群落在飞行过程中累积了生理损伤。世界各地支持多种病毒在低于临界值的人群中流行由于跨物种溢出，相关病原体在其他宿主中持续存在所需的群落规模。几种蝙蝠传播的病毒具有独特的季节性特征，与繁殖和繁殖的时间一致。相关蝙蝠宿主的营养压力，解开控制传播的机制，这些病毒在野生蝙蝠种群中的传播和持续存在在一定程度上具有重要的公共卫生意义。根据此处提出的研究计划，我们将使用分子和血清学工具来开发流行的亨尼帕病毒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果蝠，利用我们在长期野生动物监测工作中收集的样本。在马达加斯加作为人类食物来源广泛消费，以及我们研究小组的初步数据展示了全岛人类之前接触过这些人畜共患病毒的血清学特征。建议将不同的动态模型拟合到所得的人口水平数据中，以便区分这些蝙蝠宿主中季节性病毒脱落脉冲和伴随传播的机制。除了群体水平的研究外，我们还将在单个蝙蝠中构建病毒控制的宿主内模型免疫系统，我们将其与来自受 Betacoronavirus 攻击的蝙蝠的实验感染数据相匹配实验室，旨在破译激发病毒脱落的机制。同时开发蝙蝠细胞系和病毒的分子工具，以支持宿主内研究最后，我们将在人口层面和东道国内部研究的基础上进行建模和研究。实施旨在根除测试人群中循环传播的亨尼帕病毒的疫苗干预措施总的来说，我们的项目旨在利用领域、分子、以及建模工具，能够在蝙蝠病毒溢出事件发生之前进行预测和预防。