Regulation of HIV Latency by Host Cell Transcriptional and Epigenetic Networks
宿主细胞转录和表观遗传网络对 HIV 潜伏期的调节
基本信息
- 批准号:9978705
- 负责人:
- 金额:$ 38.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-16 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAddressAntiviral TherapyBackBehaviorBiological AssayCD4 Positive T LymphocytesCandidate Disease GeneCell ProliferationCell modelCellsChIP-seqCharacteristicsChromatin StructureData SetDevelopmentEnvironmentEpigenetic ProcessGene ExpressionGene Expression ProfileGene SilencingGenesGeneticGenetic TranscriptionGoalsHIVHIV InfectionsHIV-1In VitroIndividualInfectionKnowledgeLeadMaintenanceMethodologyMethodsMicroscopyModelingMolecularMonitorNaturePathway interactionsPatientsPatternPharmaceutical PreparationsPharmacologyPlayPopulationProcessProvirusesRegulationRepressionResistanceRoleTechniquesTechnologyTestingTimeTranslatingVirusWorkantiretroviral therapychromatin modificationepigenetic regulationepigenomicsexperimental studygenetic signaturehistone modificationimprovedin vivo Modelinhibitor/antagonistinsightinterestknock-downnew therapeutic targetnovelprogramsresponseselective expressionsingle cell analysissingle-cell RNA sequencingtherapeutic developmenttranscription factortranscriptomicsvirology
项目摘要
Project summary:
The existence of long-lived reservoirs of latently infected cells is recognized as a primary
barrier to a cure for HIV-1 infection. Thus, the development of therapeutic strategies to
eliminate these reservoirs is a critical scientific goal. A key problem in this field is that little is
known about the nature of latently infected cells, and the molecular mechanisms that
regulate latency. We have recently discovered that latency is associated with a distinct host
cell transcriptional signature. Our hypothesis is that this signature represents a host cell
transcriptional and epigenetic program that regulates establishment or maintenance of
latency. In the set of experiments we propose here, we will test this hypothesis directly, and
investigate the molecular mechanisms by which the host cell environment regulates
silencing of HIV transcription. This will be achieved directly testing the roles of individual
genes from the latency signature in HIV transcription. We will also undertake a detailed
analysis of epigenetic pathways that operate in latently infected cells, and directly examine
their impact on integrated proviruses. Finally, we will use cutting edge technology that
combines time-lapse microscopy and scRNAseq to discover transcriptomic features of cells
that correlate with latency reversal. Thus, this dataset will lead to new targets for
therapeutic manipulation of latency and guide further experiment to test these hypotheses in
in vitro and in vivo models of latency.
项目总结:
潜伏感染细胞的长期存活库的存在被认为是主要的
这是治愈HIV-1感染的障碍。因此,治疗策略的发展
消除这些水库是一个关键的科学目标。这个领域的一个关键问题是,几乎没有
已知潜伏感染细胞的性质,以及
规范潜伏期。我们最近发现,延迟与不同的主机相关
细胞转录签名。我们的假设是这个信号代表一个宿主细胞
转录和表观遗传程序,调节建立或维持
延迟。在我们这里提出的一系列实验中,我们将直接检验这一假设,并且
研究宿主细胞环境调节的分子机制
HIV转录沉默。这将通过直接测试个人的角色来实现
来自HIV转录中潜伏期签名的基因。我们还将进行详细的
分析在潜伏感染细胞中运行的表观遗传途径,并直接检查
它们对整合的前病毒的影响。最后,我们将使用尖端技术,
结合时间推移显微镜和scRNAseq来发现细胞的转录特征
这与潜伏期逆转有关。因此,此数据集将导致新的目标
潜伏期的治疗操作,并指导进一步的实验来验证这些假说
潜伏期的体外和体内模型。
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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Edward P Browne其他文献
PP 4.24 – 00176 Impact of cannabis use on immune cell populations and the viral reservoir in HIV-infected people on suppressive antiretroviral therapy
- DOI:
10.1016/j.jve.2022.100232 - 发表时间:
2022-12-01 - 期刊:
- 影响因子:
- 作者:
Shane D. Falcinelli;Alicia Volkheimer;Lesia Semenova;Ethan Wu;Alexander Richardson;Manickam Ashokkumar;David M Margolis;Nancie M. Archin;Cynthia D Rudin;David Murdoch;Edward P Browne - 通讯作者:
Edward P Browne
Virus-host interactions: new insights from the small RNA world
- DOI:
10.1186/gb-2005-6-11-238 - 发表时间:
2005-01-01 - 期刊:
- 影响因子:9.400
- 作者:
Edward P Browne;Junjie Li;Mark Chong;Dan R Littman - 通讯作者:
Dan R Littman
Edward P Browne的其他文献
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{{ truncateString('Edward P Browne', 18)}}的其他基金
Defining the impact of cannabinoids on the HIV reservoir in humanized mice
确定大麻素对人源化小鼠 HIV 储存库的影响
- 批准号:
10814024 - 财政年份:2023
- 资助金额:
$ 38.88万 - 项目类别:
Understanding HIV reservoir formation by profiling transcriptomic and epigenetic changes in CD4 T cells following ART initiation
通过分析 ART 启动后 CD4 T 细胞的转录组和表观遗传变化来了解 HIV 储存库的形成
- 批准号:
10759940 - 财政年份:2023
- 资助金额:
$ 38.88万 - 项目类别:
Defining the impact of cannabinoids on the latent HIV reservoir through multi-omic analysis
通过多组学分析确定大麻素对潜在 HIV 储存库的影响
- 批准号:
10219556 - 财政年份:2021
- 资助金额:
$ 38.88万 - 项目类别:
Defining the impact of cannabinoids on the latent HIV reservoir through multi-omic analysis
通过多组学分析确定大麻素对潜在 HIV 储存库的影响
- 批准号:
10622522 - 财政年份:2021
- 资助金额:
$ 38.88万 - 项目类别:
Defining the impact of cannabinoids on the latent HIV reservoir through multi-omic analysis
通过多组学分析确定大麻素对潜在 HIV 储存库的影响
- 批准号:
10433912 - 财政年份:2021
- 资助金额:
$ 38.88万 - 项目类别:
Regulation of HIV Latency by Host Cell Transcriptional and Epigenetic Networks
宿主细胞转录和表观遗传网络对 HIV 潜伏期的调节
- 批准号:
10202457 - 财政年份:2019
- 资助金额:
$ 38.88万 - 项目类别:
Regulation of HIV Latency by Host Cell Transcriptional and Epigenetic Networks
宿主细胞转录和表观遗传网络对 HIV 潜伏期的调节
- 批准号:
10425316 - 财政年份:2019
- 资助金额:
$ 38.88万 - 项目类别:
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