Project 2 - Identification of the source of viral rebound using SIV proviral genome analysis
Project 2 - Identification of the source of viral rebound using SIV proviral genome analysis
批准号:
9322142
负责人:
ROBERT F SILICIANO
金额:
$33.02万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-06-23 至 2022-05-31
关键词:
AddressAffectAnatomyAnimalsAntibodiesBiological AssayBiological MarkersBloodCD4 Positive T LymphocytesCell CompartmentationCellsClonal ExpansionDNAEvolutionFailureFrequenciesGenesGenomeHIVHIV-1InfectionInterruptionLeadLengthLightLymphoid TissueMacacaMapsMature T-LymphocyteMethodsModelingPatientsPhylogenetic AnalysisProductionProvirusesRecoveryRoleSIVSourceThymus GlandTimeTissuesViralViremiaVirionVirus Replicationcohortexperimental studygenome analysisgenome sequencinginsightintegration sitemacrophagenew technologynovelperipheral bloodpreventreconstitutionviral rebound
中文摘要
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英文摘要
Abstract
The key to developing successful strategies to delay and ultimately prevent viral rebound
upon treatment interruption is to identify the source and mechanisms of viral rebound. Ongoing
debates regarding the source of rebound include 1) whether CD4+ T cells or tissue macrophages
are the dominant source of rebound, 2) whether ongoing cycles of replication in the lymphoid
tissue contribute to rebound, 3) whether HIV-1 infection may actively drive the clonal expansion
of infected cells through integration into proliferation-related genes. We propose here to explore
these issues in collaborative studies in the SIV model using a new technology developed by our
group. Using full length, single genome sequencing of HIV-1 proviruses, we have recently shown
that the vast majority (>95%) of HIV-1 proviruses in patient cells are defective. This discovery
greatly complicates analysis of issues such as the source of rebound viremia, the possibility of
ongoing viral evolution during treatment, and the role of clonal expansion in viral persistence. In
preliminary studies, we have shown that most SIV proviruses are also defective. By focusing on
those proviruses that are not defective, we will be able to better understand the cellular sources
of viral rebound and to address controversies regarding ongoing viral replication during treatment
and reservoir expansion through proliferation of infected cells. This studies will be carried out in
conjunction with Hopkins colleagues who will employ other novel assays for replication-competent
SIV in the cohorts of treated macaques described in the application. Together these studies
should provide new insights into the sources of viral rebound.
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Administrative Core
-
批准号:10599358
-
项目类别:
-
资助金额:$1.33万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Administrative Core
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批准号:10459659
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项目类别:
-
资助金额:$40.12万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Project 1: Analysis of 2nd phase decay in persons living with HIV
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批准号:10599360
-
项目类别:
-
资助金额:$51.44万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Understanding reservoir dynamics through analysis of viral decay processes
-
批准号:10599356
-
项目类别:
-
资助金额:$157.31万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Project 1: Analysis of 2nd phase decay in persons living with HIV
-
批准号:10459661
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项目类别:
-
资助金额:$40.12万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Understanding reservoir dynamics through analysis of viral decay processes
-
批准号:10459658
-
项目类别:
-
资助金额:$160.5万
-
财政年份:2022
-
负责人:ROBERT F SILICIANO
-
依托单位:
Host and viral genomic determinants of HIV latent reservoir size and characteristics in individuals with substance use disorders
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批准号:10661843
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项目类别:
-
资助金额:$83.41万
-
财政年份:2018
-
负责人:ROBERT F SILICIANO
-
依托单位:
Host and viral genomic determinants of HIV latent reservoir size and characteristics in individuals with substance use disorders
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批准号:9764318
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项目类别:
-
资助金额:$90.9万
-
财政年份:2018
-
负责人:ROBERT F SILICIANO
-
依托单位:
Host and viral genomic determinants of HIV latent reservoir size and characteristics in individuals with substance use disorders
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批准号:10619974
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项目类别:
-
资助金额:$84.39万
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财政年份:2018
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负责人:ROBERT F SILICIANO
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依托单位:
Developmental
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批准号:8292622
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项目类别:
-
资助金额:$70.22万
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财政年份:2012
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负责人:ROBERT F SILICIANO
-
依托单位:
Define the sources of persistent HIV production
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批准号:8326896
-
项目类别:
-
资助金额:$43.37万
-
财政年份:2011
-
负责人:ROBERT F SILICIANO
-
依托单位:
Intermolecular cooperativity in the action of antiviral agents
-
批准号:8415537
-
项目类别:
-
资助金额:$26.44万
-
财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
Intermolecular cooperativity in the action of antiviral agents
-
批准号:7684577
-
项目类别:
-
资助金额:$28.7万
-
财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
Intermolecular cooperativity in the action of antiviral agents
-
批准号:8204784
-
项目类别:
-
资助金额:$28.13万
-
财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
Latent Viral Reservoirs in HIV 1 Infection
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批准号:7879719
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项目类别:
-
资助金额:$4.0万
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财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
Intermolecular cooperativity in the action of antiviral agents
-
批准号:8010968
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项目类别:
-
资助金额:$28.13万
-
财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
Intermolecular cooperativity in the action of antiviral agents
-
批准号:7759630
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项目类别:
-
资助金额:$28.41万
-
财政年份:2009
-
负责人:ROBERT F SILICIANO
-
依托单位:
HIV/SIV viral reservoirs in lymphocytes and macrophages
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批准号:7321667
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项目类别:
-
资助金额:$24.87万
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财政年份:2006
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负责人:ROBERT F SILICIANO
-
依托单位:
LOW-LEVEL HIV-1 VIREMIA IN PATIENTS ON HAART
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批准号:7200762
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项目类别:
-
资助金额:$5.58万
-
财政年份:2005
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负责人:ROBERT F SILICIANO
-
依托单位:
LOW-LEVEL HIV-1 VIREMIA IN PATIENTS ON HAART
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批准号:7044713
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项目类别:
-
资助金额:$11.71万
-
财政年份:2003
-
负责人:ROBERT F SILICIANO
-
依托单位:
海外基金