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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