Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.
非洲蝙蝠对病毒抗原的耐受性和抗性反应:人畜共患病储存宿主的免疫学权衡。
基本信息
- 批准号:10210766
- 负责人:
- 金额:$ 61.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AchievementAddressAdjuvantAfricaAfricanAntibody FormationAntiviral AgentsAreaBacterial AntigensBehaviorBehavioral MechanismsBody TemperatureCharacteristicsChiropteraCoronavirusDiseaseDisease ReservoirsDisease modelEbolaEbola Hemorrhagic FeverEbola virusEcologyEpidemiologyEquilibriumExhibitsFemaleFeverFilovirusGoalsHabitatsHumanImmuneImmune ToleranceImmune responseImmune signalingImmunologicsInfectionLeadLearningLinkMetabolicMetabolismMolecularParamyxovirusPathologyPathway interactionsPhenotypePhysiologic ThermoregulationPhysiologicalPhysiological AdaptationPhysiologyPlayPopulationPrimatesPropertyProxyRNA Virus InfectionsRNA VirusesRecording of previous eventsResistanceRetinal blind spotRiskRodentRoleSARS coronavirusSamplingSevere Acute Respiratory SyndromeSignal TransductionStudy modelsTemperatureTestingUgandaViral AntigensViral reservoirVirulentVirusVirus DiseasesVirus-like particleWorkZoonosesantigen challengeantiviral immunityexperimental studyimmune resistanceinnate immune pathwaysinnovationinsightmalaria infectionmalenovelpathogenpathogenic bacteriapathogenic viruspredicting responsepregnantpreventresponsetransmission process
项目摘要
ABSTRACT
This project focuses on understanding the role that the unique physiology of bats plays in their ability to act as
host reservoirs for diseases that can spill over to humans. The project will be carried out under field conditions
in Uganda on three species of bats that have varying links to the spread of Ebola virus (EBOV) to humans. By
comparing the ability of these three species of bats to respond to Ebola-like immune challenges, this work will
help identify the characteristics that contribute to spillover risk. In the long term, this work will help identify host
species for EBOV and other related viruses that present risk to humans. It will also help explain how different
species of bats respond to different types of viral infections. The main focus of this project will be to identify
behaviors and molecular pathways that enable reservoir hosts to tolerate infections, providing critical insight
into one of the mechanisms that leads to spillover. This work is driven by the hypothesis that some bat species
have coevolved with particular types of viral infections and, therefore, have adapted mechanisms to minimize
pathology during infection. Bats are globally biodiverse and have many unique ecological and physiological
adaptations, including flight and the ability to employ both hypo- and hyperthermic body temperature
regulation. This project focuses on three bat species chosen because they are in close contact with humans,
their habitats cover the range of EBOV exposure risk, and they have divergent coevolutionary histories with
viral pathogens; two of the three species have significant ties to EBOV epidemiology. This project addresses
these questions under natural conditions in the field by taking the innovative approach of using EBOV virus-like
particles as a proxy for experimental infection with biohazardous pathogens. This project has three specific
aims that will allow the achievement of its goals. First, the project tests the hypothesis that specific African bat
species will display signatures of EBOV disease tolerance in response to challenge with EBOV virus-like
particles, and thus are likely to be natural reservoir hosts. These experiments will provide significant insight into
disease tolerance in bats and the potential identity of EBOV reservoir(s). Second, this project tests the
hypothesis that bats display variable levels of disease tolerance that depend upon innate immune pathways
that have undergone unique evolutionary selection in bats. Third, this project explores whether tolerance of
and resistance to viral infection are facilitated by the unique metabolic behaviors of bats, namely that they can
depress metabolism and enter torpor to conserve energy and can elevate metabolism and thus temperature
during flight. The role of changes in body temperature is poorly understood and these experiments will identify
whether these physiological responses contribute to immunological tolerance and resistance in important
disease reservoirs. Together, the successful completion of these goals will help determine whether infection
tolerance confers on African bat species the ability to serve as reservoir hosts for virulent zoonotic viruses and
will identify molecular, physiological, and behavioral mechanisms that contribute to tolerance phenotypes.
摘要
这个项目的重点是了解蝙蝠的独特生理学在其作为一个生物体的能力中所起的作用。
是传染给人类的疾病的宿主该项目将在野外条件下进行
在乌干达,三种蝙蝠与埃博拉病毒(EBOV)传播给人类有不同的联系。通过
通过比较这三种蝙蝠对埃博拉样免疫挑战的反应能力,这项工作将
帮助识别导致溢出风险的特征。从长远来看,这项工作将有助于确定主机
EBOV和其他对人类构成风险的相关病毒。这也有助于解释
不同种类的蝙蝠对不同类型的病毒感染有反应。该项目的主要重点将是确定
行为和分子途径,使水库主机容忍感染,提供关键的见解,
成为导致溢出的机制之一。这项工作是由一个假设驱动的,即一些蝙蝠物种
与特定类型的病毒感染共同进化,因此,有适应机制,
感染期间的病理学蝙蝠是全球生物多样性和许多独特的生态和生理
适应,包括飞行和利用体温过低和过高的能力
调控这个项目的重点是三种蝙蝠,因为它们与人类有密切的接触,
它们的栖息地覆盖了EBOV暴露风险的范围,它们有不同的共同进化历史,
病毒病原体;三个物种中的两个与EBOV流行病学有重要联系。该项目涉及
这些问题在自然条件下的领域,通过采取创新的方法,使用EBOV病毒样
颗粒作为生物危害性病原体实验感染的代表。该项目有三个具体
这将有助于实现其目标。首先,该项目测试了一个假设,即特定的非洲蝙蝠
物种将显示EBOV疾病耐受性的特征,以响应EBOV病毒样抗原的攻击。
颗粒,因此很可能是天然的储库宿主。这些实验将提供重要的洞察力,
蝙蝠的疾病耐受性和EBOV宿主的潜在身份。其次,该项目测试了
蝙蝠表现出依赖于先天免疫途径的不同水平的疾病耐受性的假说
经历了蝙蝠独特的进化选择。第三,这个项目探讨是否容忍
和抵抗病毒感染的能力是由蝙蝠独特的代谢行为促进的,即它们可以
抑制新陈代谢,进入休眠状态,以保存能量,并能提高新陈代谢,从而提高体温
在飞行中。人们对体温变化的作用知之甚少,这些实验将确定
这些生理反应是否有助于免疫耐受性和抗性,
病源总之,这些目标的成功完成将有助于确定是否感染
耐受性赋予非洲蝙蝠物种作为有毒的人畜共患病病毒的储存宿主的能力,
将识别有助于耐受表型的分子、生理和行为机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Kenneth A Field其他文献
Kenneth A Field的其他文献
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{{ truncateString('Kenneth A Field', 18)}}的其他基金
Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.
非洲蝙蝠对病毒抗原的耐受性和抗性反应:人畜共患宿主宿主的免疫学权衡。
- 批准号:
10571935 - 财政年份:2021
- 资助金额:
$ 61.14万 - 项目类别:
Tolerance and resistance responses of African bats to viral antigens: Immunological tradeoffs in zoonotic reservoir hosts.
非洲蝙蝠对病毒抗原的耐受性和抗性反应:人畜共患宿主宿主的免疫学权衡。
- 批准号:
10360547 - 财政年份:2021
- 资助金额:
$ 61.14万 - 项目类别:
Transcriptomics of immunity and disease in African Fruit Bats- important zoonotic reservoirs
非洲果蝠——重要的人畜共患病宿主的免疫和疾病的转录组学
- 批准号:
9243490 - 财政年份:2017
- 资助金额:
$ 61.14万 - 项目类别:
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