Effect of Drugs of Abuse on CNS HIV-1 Reservoirs and Neuropathogenesis
滥用药物对中枢神经系统 HIV-1 病毒库和神经发病机制的影响
基本信息
- 批准号:10419775
- 负责人:
- 金额:$ 0.95万
- 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:2016-09-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAnatomyAnti-Retroviral AgentsAstrocytesAutomationAutopsyBiological AssayBiological ModelsBlood - brain barrier anatomyBrainCD4 Positive T LymphocytesCannabisCell Culture TechniquesCell LineCellsCocaineConsumptionDevelopmentDrug ScreeningFutureGenetic TranscriptionGoalsHIVHIV-1HumanIllicit DrugsImmunofluorescence ImmunologicIn VitroInfectionKineticsKnowledgeMeasuresMethamphetamineMethodsMicrogliaModelingNatureNeuraxisNeuropathogenesisPatientsPopulationProteinsProvirusesRNARestRoleSamplingScanningShockSolidTimeTissuesViralViral Load resultVirusbasecell typedrug of abuseestablished cell linein vitro Modelmacrophagememory CD4 T lymphocytemethamphetamine effectmethamphetamine usemonocytenovelpatient populationperipheral bloodpreventprogramsreactivation from latencyresponsesingle moleculespecific biomarkerstoolundergraduate student
项目摘要
PROJECT SUMMARY
The long term goal of this application is to study HIV-1 reservoirs that persist in CNS and to understand
the role of illicit drugs in establishing and reactivating the latent reservoirs. Persistence of latently infected cells
in CNS poses a major barrier for HIV-1 eradication. Current strategies to eliminate the latent reservoirs include
a “shock and kill” therapy and is aimed at peripheral blood, which constitutes only 1% of the total reservoirs.
Whether it is possible to envision similar strategies for the eradication of HIV-infected CNS cells is currently
unknown. In addition to the lack of knowledge about latency in CNS HIV+ cells and the effects of latency
reversing agents, illicit drugs common within the HIV-infected populations constitute a further complexity. Many
illicit drugs are known to stimulate HIV-1 replication. Since the current method to measure the peripheral blood
HIV reservoir is not applicable to solid tissues or to cells that replicate poorly such as macrophages, microglia
and astrocytes found in the brain. We have developed a novel, Single cell-single molecule, Multiplex,
Immunofluorescence (IF) and RNA FISH-based Assay (SMIRA) to detect cells in which HIV-1 is actively
replicating. Using automation, a large number of cells can be scanned. In this proposal, we will employ this novel
method to first quantitate and characterize latency in cell line models, then the latent reservoirs in brain derived
microglia and astrocytes and delineate the effect of three drugs of abuse (methamphetamine, cocaine and
cannabis) on the efficiency of formation of latent cells, the rate of reactivation of latent cells, and establishment
of latency across blood-brain-barrier (BBB). For the purpose of the summer undergraduate program, we will be
studying the role of illicit drugs on the reactivation of latently infected CNS-derived cell lines by establishing in
vitro models of latency. We will employ immortalized human monocyte and microglial cell lines to study the
kinetics of reactivation and the effect of METH using SMIRA.
项目摘要
本申请的长期目标是研究持续存在于CNS中的HIV-1储库,并了解
非法药物在建立和重新激活潜在储存库方面的作用。潜伏感染细胞的持续存在
中枢神经系统中的HIV-1感染是HIV-1根除的主要障碍。目前消除潜在水库的战略包括
这是一种“休克和杀死”疗法,针对的是外周血,而外周血仅占总储存量的1%。
目前,是否有可能设想类似的根除HIV感染的CNS细胞的策略,
未知除了缺乏关于CNS HIV+细胞中潜伏期的知识以及潜伏期的影响外,
逆转剂、艾滋病毒感染人群中常见的非法药物构成了进一步的复杂性。许多
已知非法药物会刺激HIV-1复制。由于目前测量外周血的方法
HIV储库不适用于实体组织或复制不良的细胞,如巨噬细胞、小胶质细胞
和星形胶质细胞。我们开发了一种新的,单细胞单分子,多重,
免疫荧光(IF)和基于RNA FISH的检测(SMIRA)检测HIV-1活跃的细胞
复制使用自动化,可以扫描大量细胞。在这个提案中,我们将采用这本小说
方法首先定量和表征细胞系模型中的潜伏期,然后导出大脑中的潜伏库
小胶质细胞和星形胶质细胞,并描绘了三种药物滥用(甲基苯丙胺,可卡因和
大麻)对潜伏细胞的形成效率、潜伏细胞的再活化速率和建立
血脑屏障(BBB)的潜伏期。为了夏季本科课程的目的,我们将
研究非法药物对潜在感染的CNS衍生细胞系的重新激活的作用,
潜伏期的体外模型。我们将使用永生化的人单核细胞和小胶质细胞系来研究
使用SMIRA的再活化动力学和METH的影响。
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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GANJAM V KALPANA其他文献
GANJAM V KALPANA的其他文献
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{{ truncateString('GANJAM V KALPANA', 18)}}的其他基金
RNA-mimicry to guide the intra-cellular targeting of host virus protein and viral RNA-protein interactions to inhibit HIV replication.
RNA模拟引导宿主病毒蛋白的细胞内靶向和病毒RNA-蛋白相互作用以抑制HIV复制。
- 批准号:
10554025 - 财政年份:2022
- 资助金额:
$ 0.95万 - 项目类别:
RNA-mimicry to guide the intra-cellular targeting of host virus protein and viral RNA-protein interactions to inhibit HIV replication.
RNA模拟引导宿主病毒蛋白的细胞内靶向和病毒RNA-蛋白相互作用以抑制HIV复制。
- 批准号:
10618961 - 财政年份:2022
- 资助金额:
$ 0.95万 - 项目类别:
Single cell RNA-seq and single molecule RNA-FISH approaches to study stochasticity of latent HIV-1 reactivation
单细胞 RNA-seq 和单分子 RNA-FISH 方法研究潜在 HIV-1 重新激活的随机性
- 批准号:
10082908 - 财政年份:2020
- 资助金额:
$ 0.95万 - 项目类别:
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- 批准号:
10302316 - 财政年份:2020
- 资助金额:
$ 0.95万 - 项目类别:
Mechanism of HIV-1 Latency and Reactivation Kinetics Using Single Cell Analysis
使用单细胞分析研究 HIV-1 潜伏期和再激活动力学的机制
- 批准号:
9298589 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
Effect of drugs of abuse on CNS HIV-1 reservoirs and neuropathogenesis
滥用药物对 CNS HIV-1 储存库和神经发病机制的影响
- 批准号:
9532834 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
Effect of drugs of abuse on CNS HIV-1 reservoirs and neuropathogenesis
滥用药物对 CNS HIV-1 储存库和神经发病机制的影响
- 批准号:
9333307 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
Effect of drugs of abuse on CNS HIV-1 reservoirs and neuropathogenesis
滥用药物对 CNS HIV-1 储存库和神经发病机制的影响
- 批准号:
9977143 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
Mechanism of HIV-1 Latency and Reactivation Kinetics Using Single Cell Analysis
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- 批准号:
9207956 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
Effect of drugs of abuse on CNS HIV-1 reservoirs and neuropathogenesis
滥用药物对 CNS HIV-1 储存库和神经发病机制的影响
- 批准号:
9926378 - 财政年份:2016
- 资助金额:
$ 0.95万 - 项目类别:
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