Recognition of HIV by the Inflammasome Signaling Complex
炎症小体信号复合体对 HIV 的识别
基本信息
- 批准号:9319096
- 负责人:
- 金额:$ 19.63万
- 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:2013-08-15 至 2019-07-31
- 项目状态:已结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAdaptor Signaling ProteinAddressAgeAnti-Inflammatory AgentsAnti-inflammatoryAntiviral ResponseBacterial InfectionsBindingCardiovascular DiseasesCell LineageCellsChronicChronic Kidney FailureComplexCytoplasmDetectionDevelopmentDiabetes MellitusDiseaseDisease OutcomeEndocrine System DiseasesEndocytosisEndosomesEngineeringEnvironmentEventFutureGenetic TranscriptionHIVHIV InfectionsHIV-1Highly Active Antiretroviral TherapyImmune responseImmunosuppressionIncidenceIndividualInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInterferon Type IInterleukin-1Interleukin-18InterventionInvadedKidney DiseasesLactamaseLigandsLiver diseasesLongevityLysosomesMalignant NeoplasmsMeasuresMedicalMethodsModelingMorbidity - disease rateOsteoporosisPathogenesisPersonsPlasmaPreparationProcessProductionQuantitative Reverse Transcriptase PCRRNA InterferenceRNA VirusesRiskRoleSignal PathwaySignal TransductionStimulusSumSystemTNF geneTestingTherapeutic InterventionToll-like receptorsViralVirionVirusVirus DiseasesWorkcytokineextracellularimmune activationimprovedinhibitor/antagonistmicrobialmonocytemortalitynervous system disordernovelpathogenpublic health relevanceresponseuptake
项目摘要
DESCRIPTION (provided by applicant): HIV infection causes significant morbidity and mortality worldwide. Highly active antiretroviral therapy has dramatically reduced the risk of AIDS, opportunistic illnesses and mortality directly related to immune suppression. However, with the increased longevity of HIV infected persons, it is now evident that they are at increased risk of developing a variety of non-AIDS conditions including cardiovascular, renal, endocrine and neurologic diseases. A growing body of evidence implicates chronic inflammation and immune activation in the development of these non-AIDS conditions. We have shown that inflammasome activation as measured by interleukin-18 (IL-18) production occurs during both HIV and other chronic viral infections. Plasma from infected subjects as well as purified virus preparations stimulate monocytes to produce IL-18. We hypothesize that such viruses induce chronic low-level immune activation by sustaining abnormal inflammasome activity in monocyte lineage cells. This proposal addresses the mechanism by which RNA viruses capable of establishing chronic infections stimulate the inflammasome complex in monocytes regardless of whether they directly infect these cells. We will (1) determine whether Toll-like receptors, which have been previously shown to activate inflammasomes during bacterial infection, also recognize and activate inflammasomes during viral infections. (2) We will examine how the extracellular cytokine environment alters inflammasome activity and; (3) study the role of virus uptake by endocytosis in inflammasome activation. This work will enhance our understanding of immune activation caused by these important viruses. A clear understanding of this process will have implications for managing and treating both the primary viral infection and the co-morbid medical conditions, which are often exacerbated by prolonged immune activation.
描述(由申请人提供):HIV感染在全球范围内引起明显的发病率和死亡率。高度活跃的抗逆转录病毒疗法已大大降低了与免疫抑制直接相关的艾滋病,机会性疾病和死亡率的风险。但是,随着艾滋病毒感染者的寿命增加,现在很明显,他们患有多种非AID疾病的风险增加,包括心血管,肾脏,内分泌和神经系统疾病。越来越多的证据表明,在这些非AIDS条件的发展中,慢性炎症和免疫激活。我们已经表明,在HIV和其他慢性病毒感染期间,通过白介素-18(IL-18)的产生测量的炎性体激活发生。感染受试者以及纯化的病毒制剂的血浆刺激单核细胞产生IL-18。我们假设这种病毒通过在单核细胞谱系细胞中维持异常的炎性体活性来诱导慢性低水平免疫激活。该提案解决了RNA病毒能够建立慢性感染的机制,无论它们是否直接感染了这些细胞,都可以刺激单核细胞中的炎性体复合物。我们将(1)确定先前已证明在细菌感染期间激活炎症的收费样受体,在病毒感染期间还识别和激活炎症。 (2)我们将研究细胞外细胞因子环境如何改变炎症体的活性; (3)研究内吞作用在炎症体激活中摄取病毒的作用。这项工作将增强我们对这些重要病毒引起的免疫激活的理解。对这一过程的明确理解将对管理和治疗主要的病毒感染和合并症状况有影响,这些病情通常会因长期的免疫激活而加剧。
项目成果
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Michael Anand Chattergoon其他文献
Michael Anand Chattergoon的其他文献
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{{ truncateString('Michael Anand Chattergoon', 18)}}的其他基金
Recognition of HIV by the Inflammasome Signaling Complex
炎症小体信号复合体对 HIV 的识别
- 批准号:
8720683 - 财政年份:2013
- 资助金额:
$ 19.63万 - 项目类别:
Recognition of HIV by the Inflammasome Signaling Complex
炎症小体信号复合体对 HIV 的识别
- 批准号:
8603101 - 财政年份:2013
- 资助金额:
$ 19.63万 - 项目类别:
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Recognition of HIV by the Inflammasome Signaling Complex
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- 资助金额:
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Recognition of HIV by the Inflammasome Signaling Complex
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