Role for polyamines in Ebola Virus Replication
Role for polyamines in Ebola Virus Replication
批准号:
9018817
负责人:
John H Connor
金额:
$24.63万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-02-01 至 2018-01-31
关键词:
AddressAdvanced DevelopmentAmino AcidsAnimal Disease ModelsAnimal ModelAnimalsAntiviral TherapyBiochemistryBiologyCell physiologyCellsCellular biologyChargeClinicDNA VirusesDataDependenceDiseaseDisease OutbreaksDrug TargetingEbola Hemorrhagic FeverEbola virusEbola-like VirusesEffectivenessElongation FactorEnzymesExcisionFDA approvedFamilyFatality rateFiloviridaeFilovirusFrankfurt-Marburg Syndrome VirusGene ExpressionGene TargetingGenesGeneticGoalsHealthHumanIn VitroInfectionIntegration Host FactorsLeadLinkMagicMammalian CellPanicPathogenesisPathway interactionsPlayPolyaminesPolymeraseProcessProtein BiosynthesisProteinsRetroviridaeRoleSatellite VirusesStructureSystemTechnologyTestingTheftTherapeuticTranslationsVaccinesVeinsViralViral GenesVirusVirus ReplicationWestern AfricaWorkbasecancer cellcombateIF-5Ahypusinein vivoinsightknock-downmolecular targeted therapiespathogenpublic health relevanceresearch studysmall moleculestemtreatment programvirus host interaction
中文摘要
英文摘要
DESCRIPTION (provided by applicant): The Filoviridae are a small family of viruses that include the highly pathogenic Ebola and Marburg viruses. These viruses are associated with fatality rates of up to 90%. As has been highlighted during the recent outbreaks of Ebola in Western Africa, filoviruses have tremendous potential for adverse health effects both directly (through direct pathogenesis) and indirectly (forcing the shutdown of existing clinics and treatment programs, sparking panic). Though a variety of potential therapies for the disease have been developed and deployed, it is currently unclear which if any have helped. A clear lesson from the outbreak is that the lack of basic information about viruses like Ebola have hampered effective control and therapy. In this vein, it is clear that basic aspects of how Ebola and its relatives utilize components of infected cells to their advantage are still unknown. A detailed understanding of how Ebola "steals" from its host or identification of cellular processes that the virus requires can offer important insight into both the general biology of the virus and can lead to the identification of host processes that can be effectively targeted to block viral replication. This proposal will test the hypothesis that polyamines and products of polyamines such as the non-canonical amino acid hypusine are essential for Ebola virus replication. To test this hypothesis we will use existing small- molecules that target the polyamine synthesis pathway and we will use gene-targeting knockdown technology to assess the importance of polyamine synthesis enzymes, hypusination enzymes and the hypusinated protein eIF5A on Ebola virus gene expression. Through these studies we hope to determine the importance of this pathway for viral gene expression and understand the mechanism by which the polyamine pathway controls viral gene expression. Identification of this pathway as important for Ebola virus replication has significant translational implications, as there are many compounds that are known to target the polyamine and hypusine synthesis pathways. Some of these are FDA-approved, some are in advanced development. Data supporting our hypothesis that this pathway is important can lead to the testing of these compounds in animal models of disease.
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资助金额:$83.62万
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财政年份:2011
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Stage-Specific Inhibitors of Orthopoxviruses
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批准号:8257919
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项目类别:
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资助金额:$4.09万
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财政年份:2011
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负责人:John H Connor
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依托单位:
Development of Near Real-Time, Multiplexed Diagnostics for Viral Hemorrhagic Feve
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批准号:8302193
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项目类别:
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资助金额:$99.18万
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财政年份:2011
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负责人:John H Connor
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依托单位:
Development of Near Real-Time, Multiplexed Diagnostics for Viral Hemorrhagic Feve
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批准号:8711239
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项目类别:
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资助金额:$87.26万
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财政年份:2011
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依托单位:
Development of Near Real-Time, Multiplexed Diagnostics for Viral Hemorrhagic Feve
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批准号:8184838
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资助金额:$142.23万
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财政年份:2011
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负责人:John H Connor
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依托单位:
New Ops-Proof of Concept Studies on a Class of Broad Spectrum Antiviral Compounds
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批准号:7942397
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项目类别:
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资助金额:$17.08万
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财政年份:2009
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负责人:John H Connor
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依托单位:
New Ops: Proof of concept studies on a class of broad spectrum antiviral compound
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批准号:7645451
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项目类别:
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资助金额:$23.29万
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财政年份:2008
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负责人:John H Connor
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依托单位:
Control of elF4F complex by Vesicular Stomatitis Virus
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批准号:7228127
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项目类别:
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资助金额:$10.8万
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财政年份:2006
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负责人:John H Connor
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依托单位:
Control of elF4F complex by Vesicular Stomatitis Virus
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批准号:6909396
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项目类别:
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资助金额:$16.2万
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财政年份:2006
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负责人:John H Connor
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依托单位:
Protein synthesis control by vesicular stomatits virus
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批准号:6706264
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项目类别:
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资助金额:$2.05万
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财政年份:2003
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负责人:John H Connor
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依托单位:
Protein synthesis control by vesicular stomatits virus
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批准号:6584023
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项目类别:
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资助金额:$4.62万
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财政年份:2003
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负责人:John H Connor
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依托单位:
海外基金