HIV-a Persistence in Myeloid Cell Reservoirs
HIV-a Persistence in Myeloid Cell Reservoirs
批准号:
9204094
负责人:
Mario Stevenson
金额:
$19.19万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2018-06-30
关键词:
AIDS/HIV problemAlveolarAlveolar MacrophagesAnatomyAntiviral AgentsAttentionBiological AssayCD4 Positive T LymphocytesCell surfaceCellsDNAEvaluationFrequenciesGenomeGut associated lymphoid tissueHIVHIV-1IndividualInfectionInterruptionLungLymphoidLymphoid TissueMacacaModelingMyeloid CellsPhagocytosisPhylogenetic AnalysisPlasmaPlayPopulationPropertyProvirusesRNAResearchRoleSIVSamplingSurveysTimeTissuesTropismVariantViralViral GenomeViral reservoirViremiaVirusVirus DiseasesWorkantiretroviral therapycatalystcell envelopedeep sequencingdesigndigitalfallsinsightlymph nodesmacrophagememory CD4 T lymphocyteviral DNAviral RNAvirus tropism
中文摘要
项目总结:
英文摘要
Project Summary:
As the HIV/AIDS research field embarks on an endeavor to cure HIV-1 infection, insight into the obstacles to
curing infection are essential. While most of the attention in this regard has focused on CD4+ T-cell reservoirs,
far less attention has focused on whether tissue macrophages are a reservoir in HIV-1-infected individuals on
suppressive antiretroviral therapy (ART). Indeed, the question of macrophage reservoirs has been polarized by
recent work arguing that viral DNA in macrophages is exclusively a consequence of phagocytosis of infected
CD4+ T-cells (Calantone et al., 2014). As a result, research on myeloid cell reservoirs is falling into obscurity.
Infection of macrophages can only be initiated by HIV-1 variants that have the ability to use low levels of CD4
on the cell surface. We therefore propose to reveal myeloid cell reservoirs by the presence of macrophage-tropic
envelopes from DNA and cell-associated RNA obtained from lymphoid tissues of ART-suppressed individuals
and from the earliest recrudescing viruses obtained from individuals undergoing analytic treatment interruption
(ATI). This unbiased approach does not rely on purification of myeloid cells to homogeneity nor is it obfuscated
by the presence of phagocytosed CD4+ T-cells. To further validate myeloid cells as functional reservoirs, we will
attempt to directly demonstrate the existence of macrophage-tropic, replication-competent virus in an accessible,
macrophage-rich anatomic compartment.
Specifically, we propose to:
Aim 1: Identify macrophage-tropic variants in lymphoid tissue (LN, GALT) from ART-suppressed
individuals and in early recrudescing variants following ATI. We will employ a semi-high throughput tropism
assay, capable of identifying low-frequency, macrophage-tropic viruses to infer the existence of a macrophage
reservoir.
Aim 2: Establish whether alveolar macrophages support HIV-1 persistence in individuals on suppressive
ART. Tropism and phylogenetic relationships between virus populations in alveolar macrophages and CD4+ T-
cells from aviremic individuals will be assessed as well as isolation of macrophage-tropic virus from alveolar
macrophages ex vivo
These studies should, for the first time, provide definitive evidence for a viral reservoir in tissue macrophages
and as such, provide the catalyst for the design of strategies to clear macrophage reservoirs and increase the
likelihood of curing infection.
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专著(0)
科研奖励(0)
会议论文
Irreversible Proviral Silencing in Myeloid Cells
-
批准号:10705469
-
项目类别:
-
资助金额:$19.19万
-
财政年份:2023
-
负责人:Mario Stevenson
-
依托单位:
Simple Method for Screening of HIV Drug Resistance in Resource-Limited Settings
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批准号:10384759
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项目类别:
-
资助金额:$30.0万
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财政年份:2022
-
负责人:Mario Stevenson
-
依托单位:
Defining a Role for Liver Myeloid Cells in Viral Persistence under ART-SUPPLEMENT 1
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批准号:10852118
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项目类别:
-
资助金额:$6.02万
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财政年份:2022
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负责人:Mario Stevenson
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依托单位:
Defining a Role for Liver Myeloid Cells in Viral Persistence under ART
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批准号:10527635
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项目类别:
-
资助金额:$46.95万
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财政年份:2022
-
负责人:Mario Stevenson
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依托单位:
Defining a Role for Liver Myeloid Cells in Viral Persistence under ART
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批准号:10654037
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项目类别:
-
资助金额:$51.04万
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财政年份:2022
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负责人:Mario Stevenson
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依托单位:
Revealing HIV-1 persistence in myeloid cell reservoirs
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批准号:10709063
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项目类别:
-
资助金额:$53.83万
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财政年份:2018
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负责人:Mario Stevenson
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依托单位:
Revealing HIV-1 persistence in myeloid cell reservoirs
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批准号:10319986
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项目类别:
-
资助金额:$38.38万
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财政年份:2018
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负责人:Mario Stevenson
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依托单位:
Reservoir activity and recrudescent virus composition in HIV and SIV rebound
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批准号:10205971
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项目类别:
-
资助金额:$29.59万
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财政年份:2017
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负责人:Mario Stevenson
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依托单位:
Reservoir activity and recrudescent virus composition in HIV and SIV rebound
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批准号:9332149
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项目类别:
-
资助金额:$34.19万
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财政年份:2017
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists - Project 2
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批准号:8723304
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项目类别:
-
资助金额:$30.55万
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财政年份:2014
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists - Core A
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批准号:8723306
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项目类别:
-
资助金额:$4.9万
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财政年份:2014
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负责人:Mario Stevenson
-
依托单位:
Preclinical Development of HIV-1 Vif Antagonists - Core A
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批准号:8656186
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项目类别:
-
资助金额:$4.9万
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财政年份:2013
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists
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批准号:8904721
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项目类别:
-
资助金额:$119.44万
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财政年份:2013
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists
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批准号:9325570
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项目类别:
-
资助金额:$116.85万
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财政年份:2013
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists
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批准号:8541369
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项目类别:
-
资助金额:$126.23万
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财政年份:2013
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负责人:Mario Stevenson
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依托单位:
Preclinical Development of HIV-1 Vif Antagonists
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批准号:8723302
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项目类别:
-
资助金额:$123.75万
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财政年份:2013
-
负责人:Mario Stevenson
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依托单位:
The role of myeloid cells in viral replication, persistence and neuroinvasion
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批准号:8840999
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项目类别:
-
资助金额:$35.82万
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财政年份:2011
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负责人:Mario Stevenson
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依托单位:
The International Workshop on HIV Persistence During Therapy
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批准号:8210430
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项目类别:
-
资助金额:$2.0万
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财政年份:2011
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负责人:Mario Stevenson
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依托单位:
ADM CORE
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批准号:8271415
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项目类别:
-
资助金额:$5.63万
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财政年份:2011
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负责人:Mario Stevenson
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依托单位:
The International Workshop on HIV Persistence During Therapy
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批准号:8688890
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Mario Stevenson
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依托单位:
海外基金