Subversion of Autophagy Pathway and Constituents by RNA viruses
RNA病毒对自噬途径和成分的颠覆
基本信息
- 批准号:8697258
- 负责人:
- 金额:$ 46.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-08-06 至 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntiviral AgentsApoptosisApoptoticAutophagocytosisAutophagosomeAxonBiochemicalBiologicalBiological AssayCell physiologyCellsCoxsackie VirusesCytolysisCytoplasmic StructuresDNA Sequence RearrangementDefectDengueDengue VirusDependenceEatingEukaryotic CellEyeFamily PicornaviridaeGeneticGenomeGoalsGrowthHepatitis AHepatitis A VirusHuman poliovirusImmune responseInfectionIntracellular MembranesKnock-outLifeLipidsLiposomesLiverLongevityLyticMaintenanceMammalsMembraneMembrane BiologyMicrobeMicroscopyMonitorMorphogenesisMorphologyMusMutationNeuronsNutritionalOptic NervePathway interactionsPharmacologic SubstancePicornaviridae InfectionsPoliovirusesProcessProteinsRNARNA VirusesResearchRhinovirusRoleSARS coronavirusSiteSorting - Cell MovementStarvationSupplementationSurfaceTestingTimeTravelVesicleViralViral ProteinsVirionVirusVirus DiseasesWest Nile virusinhibitor/antagonistmacromoleculenovelpathogenprotein aggregateresearch studyresponsesynucleintime usetissue culturetissue/cell culturetumorviral RNA
项目摘要
DESCRIPTION (provided by applicant): Positive-strand RNA viruses that infect eukaryotic cells all rearrange intracellular membranes and replicate their RNA genomes on the topologically cytoplasmic surfaces. Several of these viruses, including poliovirus and Dengue virus, mimic or subvert the cellular pathway of autophagy to form double-membraned intracellular compartments. Experiments are proposed to explore the hypothesis that these membranes facilitate viral exit from infected cells: for poliovirus, because the double-membraned topology can allow non-lytic exit of virus and other cytoplasmic constituents, and for Dengue virus, because the pathway or products of cellular autophagy are required for infectious virion assembly. To investigate the contribution of double-membraned vesicles during poliovirus infection of tissue-culture cells and mice, live-cell time-lapse microscopy, pharmaceutical perturbations, and viral and mouse genetics are employed to distinguish between lytic and non-lytic, and between apoptotic and non-apoptotic spread. These principles are also applied to the study of hepatitis A virus, a picornavirus whose ability to spread through the liver with no apparent cell lysis remains mysterious and may be explained by the topology of the double-membraned vesicles induced during infection. A single poliovirus protein, 3AB, was found to be sufficient to create double-membraned from single-membraned liposomes, and the hypothesis that this mechanism might be shared with cellular autophagy proteins tested. The novel and dramatic dependence of Dengue virus infectivity on a functioning cellular autophagy pathway will be explored mechanistically by determining the biochemical defect in the non-infectious virions produced when cellular autophagy is inhibited. The versatile cellular process of autophagy, although known to be part of the innate immune response, provides a new target for antiviral control.
描述(由申请人提供):感染真核细胞的正链RNA病毒均会重排细胞内膜,并在拓扑学上的细胞质表面复制其RNA基因组。这些病毒中的一些,包括脊髓灰质炎病毒和登革病毒,模仿或破坏自噬的细胞途径以形成双膜细胞内区室。提出实验来探索这些膜促进病毒从感染细胞中退出的假设:对于脊髓灰质炎病毒,因为双膜拓扑结构可以允许病毒和其他细胞质成分的非裂解退出,而对于登革病毒,因为细胞自噬的途径或产物是感染性病毒体组装所必需的。为了研究脊髓灰质炎病毒感染组织培养细胞和小鼠期间双膜囊泡的贡献,采用活细胞延时显微镜、药物扰动以及病毒和小鼠遗传学来区分裂解和非裂解,以及凋亡和非凋亡扩散。这些原则也适用于甲型肝炎病毒的研究,一种小核糖核酸病毒,其通过肝脏传播而没有明显的细胞裂解的能力仍然是神秘的,可以通过感染过程中诱导的双膜囊泡的拓扑结构来解释。发现单个脊髓灰质炎病毒蛋白3AB足以从单膜脂质体产生双膜脂质体,并且该机制可能与细胞自噬蛋白共享的假设被测试。登革病毒感染性对功能性细胞自噬途径的新颖和戏剧性的依赖性将通过确定细胞自噬被抑制时产生的非感染性病毒体中的生化缺陷来机械地探索。自噬的多功能细胞过程,虽然已知是先天免疫反应的一部分,但提供了抗病毒控制的新靶点。
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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Karla Kirkegaard其他文献
Karla Kirkegaard的其他文献
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{{ truncateString('Karla Kirkegaard', 18)}}的其他基金
Viral use and mimicry of autophagy pathway and components
自噬途径和成分的病毒利用和模拟
- 批准号:
9975099 - 财政年份:2018
- 资助金额:
$ 46.63万 - 项目类别:
Viral use and mimicry of autophagy pathway and components
自噬途径和成分的病毒利用和模拟
- 批准号:
9757678 - 财政年份:2018
- 资助金额:
$ 46.63万 - 项目类别:
Viral use and mimicry of autophagy pathway and components
自噬途径和成分的病毒利用和模拟
- 批准号:
10215472 - 财政年份:2018
- 资助金额:
$ 46.63万 - 项目类别:
Inhibiting Cellular Autophagy to Thwart Dengue Virus Packaging and Replication
抑制细胞自噬以阻止登革热病毒包装和复制
- 批准号:
8505375 - 财政年份:2012
- 资助金额:
$ 46.63万 - 项目类别:
Inhibiting Cellular Autophagy to Thwart Dengue Virus Packaging and Replication
抑制细胞自噬以阻止登革热病毒包装和复制
- 批准号:
8391666 - 财政年份:2012
- 资助金额:
$ 46.63万 - 项目类别:
The cell biology of Theiler's virus persistence in CNS
泰勒病毒在中枢神经系统中持续存在的细胞生物学
- 批准号:
7244401 - 财政年份:2006
- 资助金额:
$ 46.63万 - 项目类别:
The Cell Biology of Theiler's Virus Persisstence in CNS
泰勒病毒在中枢神经系统中持续存在的细胞生物学
- 批准号:
7144321 - 财政年份:2006
- 资助金额:
$ 46.63万 - 项目类别:
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