Quantitative mapping of interactions between dengue virus and its hosts
登革热病毒与其宿主之间相互作用的定量图谱
基本信息
- 批准号:8918261
- 负责人:
- 金额:$ 5.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-01-01 至 2016-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffinity ChromatographyArbovirusesArthropod VectorsBiochemical ProcessCell physiologyCellsCharacteristicsChromosome MappingCollaborationsComplementComplexCoupledCulicidaeDataDefectDendritic CellsDengueDengue InfectionDengue VirusDistantEvolutionGenesGeneticGenetic studyHabitatsHumanIntegration Host FactorsLinkMapsMass Spectrum AnalysisMeasuresMolecularOntologyPathway interactionsPhenotypeProteinsRNA InterferenceRNA chemical synthesisReporterReportingResistanceScientistStagingSystemTherapeuticTranslationsVertebratesVirusVirus Replicationcombatcomparativedrug developmentfunctional groupgenetic approachinsightknock-downmonocytepathogenprophylacticpublic health relevanceresearch studytherapeutic developmenttransmission processvector mosquitovirus host interaction
项目摘要
DESCRIPTION (provided by applicant): Viruses interact with the host to orchestrate myriad biochemical processes required for replication. A unique characteristic of arboviruses such as dengue virus (DENV), which are transmitted to vertebrates by arthropod vectors, is that these viruses must maintain interactions in two evolutionarily distant hosts to successfully replicate. I this proposal, comparative genetic interaction mapping will be used to identify conserved host factors that are functionally important for DENV replication: Aim 1-Quantitatively map evolutionary constraints of DENV-host interactions A genetic interaction between two factors implies that they are functionally related. Single and pairwise RNAi knockdown coupled with a reporter virus system will be used to quantitatively map genetic interactions of host factors that physically interact with DENV. This will be the first systematic study of genetic interactions in a
host-pathogen system. Hierarchical clustering will be applied to the data generated in Aim 1 to identify host factors with similar genetic interaction profiles. Previously acquired DENV-host and host-host protein interaction data will be incorporated to define functional modules. Enrichment analysis will be used to identify functional groups and pathways that are enriched for host replication or restriction factors. The results from Aim 1 will address fundamental questions regarding the evolutionary constraints imposed by hosts on DENV replication. Aim 2-Identify the point of defect in the viral replication cycle for a subset of host replication factors from conserved functional modules Viral replication will be measured at the point of translation, RNA synthesis and exit in both host systems following knockdown by RNAi for 10 host replication factors from conserved functional modules characterized in Aim 1. The experiments in this aim will provide insight into the molecular mechanism of DENV replication in two evolutionarily distant hosts. Ultimately, an evolutionary perspective on DENV-host interactions will be particularly useful for drug development. Targeting conserved or evolutionarily constrained interactions will yield more robust therapies, as DENV will be limited in its ability to evolve resistance.
描述(由申请人提供):病毒与宿主相互作用,协调复制所需的无数生化过程。通过节肢动物媒介传播给脊椎动物的登革热病毒(DENV)等虫媒病毒的一个独特特征是,这些病毒必须在两个进化上相距遥远的宿主中保持相互作用才能成功复制。在本研究中,比较遗传相互作用作图将用于鉴定对DENV复制具有重要功能的保守宿主因子。目的1:定量绘制DENV-宿主相互作用的进化约束。两个因子之间的遗传相互作用意味着它们在功能上是相关的。单个和成对的RNAi敲除与报告病毒系统结合将用于定量绘制与DENV物理相互作用的宿主因子的遗传相互作用。这将是第一次系统地研究遗传相互作用
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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Priya Shirish Shah其他文献
Priya Shirish Shah的其他文献
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{{ truncateString('Priya Shirish Shah', 18)}}的其他基金
Molecular mechanisms linking viral replication and neuropathogenesis
连接病毒复制和神经发病机制的分子机制
- 批准号:
10660340 - 财政年份:2023
- 资助金额:
$ 5.8万 - 项目类别:
Molecular mechanisms linking viral replication and neuropathogenesis
连接病毒复制和神经发病机制的分子机制
- 批准号:
10673233 - 财政年份:2022
- 资助金额:
$ 5.8万 - 项目类别:
Conserved molecular mechanisms of replication for mosquito-borne flaviviruses
蚊媒黄病毒复制的保守分子机制
- 批准号:
10431689 - 财政年份:2022
- 资助金额:
$ 5.8万 - 项目类别:
Conserved molecular mechanisms of replication for mosquito-borne flaviviruses
蚊媒黄病毒复制的保守分子机制
- 批准号:
10577854 - 财政年份:2022
- 资助金额:
$ 5.8万 - 项目类别:
A vertebrate model of viral and hereditary microcephaly
病毒和遗传性小头畸形的脊椎动物模型
- 批准号:
10576107 - 财政年份:2022
- 资助金额:
$ 5.8万 - 项目类别:
Quantitative mapping of interactions between dengue virus and its hosts
登革热病毒与其宿主之间相互作用的定量图谱
- 批准号:
8783961 - 财政年份:2015
- 资助金额:
$ 5.8万 - 项目类别:
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