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
项目成果
期刊论文数量(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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