Targeting HIV persistence in CD4+ T memory stem cells
靶向 CD4 T 记忆干细胞中的 HIV 持久性
基本信息
- 批准号:9321252
- 负责人:
- 金额:$ 42.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-10 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAgreementAnti-Retroviral AgentsAntiviral AgentsAntiviral TherapyArchitectureBiologyCD4 Positive T LymphocytesCell Culture TechniquesCell LineageCellsCharacteristicsCollaborationsCytometryDNADataDiseaseEngineeringEventFrequenciesGenerationsGeneticGenetic TranscriptionGenomeGenomicsGoalsHDAC1 geneHIVHIV InfectionsHIV SeropositivityHighly Active Antiretroviral TherapyHumanIL2 geneImmuneImmunologic SurveillanceInfectionInfection ControlIntegration Host FactorsInterleukin-15InterventionKnowledgeLaboratoriesLifeMaintenanceMeasuresMemoryModelingMolecularMolecular ProbesNuclearOligonucleotidesOutcomePathogenesisPathway interactionsPatientsPersonsPhysiologicalPlayPopulationProliferatingPropertyProteinsProteomeProteomicsProvirusesReporterResearchReverse TranscriptionRoleSIVSeedsSignal TransductionSourceStem cellsT memory cellT-LymphocyteTestingTherapeuticTimeViralVirusVirus Diseasesbasecytokinegenetic makeupin vivoinhibitor/antagonistinnovationmemory CD4 T lymphocytenoveloffspringprogramspublic health relevancepurgeresearch studyself-renewalstemvolunteer
项目摘要
DESCRIPTION (provided by applicant): Eliminating HIV persistence is an obligated step to curing HIV/AIDS disease. Indeed, life-long highly active antiretroviral therapy is required since current antiviral drugs fail to eliminate the virus from HIV-infected patients. Despite intensive research there are no effective strategies to eliminate latent, transcriptionally silent HIV proviruses from HIV infected patients with well-controlled HIV infection. Emerging evidence suggest that CD4+ T memory stem cells (TSCM), the least differentiated of all CD4+ T cell memory populations, support HIV infection. There remains, however, a fundamental gap in our knowledge regarding the mechanisms and the extent of the impact of CD4+ T cells with stem like properties (TSMC) on establishment of HIV latency and persistence. Our preliminary data suggests that TSCM are fundamentally different from other CD4+ T memory cells. Since stem cells can renew and generate progeny cells for prolonged periods, we hypothesize that infected TSCM persist, maintain and seed CD4 T cells carrying latent proviruses. We will use mass-cytometry, 3D-FISH, proteomics and genomics to probe for the molecular mechanisms of latency establishment and maintenance specific for primary human CD4 T stem cells. We will define correlates of abortive, silent and productive infections in CD4+ TSCM, define the cellular programs specific for HIV persistence in CD4+ TSCM and probe for the CD4+ TSCM reservoir in HIV positive patients with spontaneous or HAART-assisted control of HIV infection. We will test to what extent a small number of integrations can seed the reservoir carrying the same latent provirus over multiple cell generations. Understanding the molecular mechanisms underlying latency establishment and maintenance in CD4+ TSCM is essential to develop targeted interventions aimed at shrinking and purging HIV persistence in CD4+ TSCM.
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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Viviana A Simon其他文献
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$ 42.38万 - 项目类别:
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8651884 - 财政年份:2013
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$ 42.38万 - 项目类别:
HTLV-1 antagonists of HIV restriction factors
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8466151 - 财政年份:2013
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