Characterization of a New Anti-HIV Immune Protein
Characterization of a New Anti-HIV Immune Protein
批准号:
9349402
负责人:
JAY A LEVY
金额:
$23.78万
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:
2017-03-06 至 2019-02-28
关键词:
AIDS preventionAdenovirusesAdverse effectsAlpha CellAnti-Retroviral AgentsAntiviral AgentsAntiviral ResponseApoptosisBackBinding ProteinsBinding SitesBlocking AntibodiesBloodCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCRISPR/Cas technologyCell Surface ProteinsCell Surface ReceptorsCell SurvivalCell surfaceCellsCleaved cellComplementary DNACytomegalovirusDNA Microarray ChipDevelopmentDiseaseDrug TargetingEmbryoFlow CytometryGene ExpressionGenesGenetic TranscriptionHIVHIV InfectionsHIV resistanceHourHumanImmuneImmune responseImmunologicsImmunotherapyIndividualInfectionInfection preventionIntegral Membrane ProteinLengthLigandsLinkLong-Term SurvivorsMediatingMembraneMitogen-Activated Protein KinasesModelingNF-kappaB-inducing kinasePathway interactionsPatientsPilot ProjectsPoliomyelitisPrimatesProceduresProcessProtein IsoformsProteinsPublic HealthRNARecoveryRecruitment ActivityResearch PersonnelResistanceRetroviral VectorReverse Transcriptase Polymerase Chain ReactionRoleSIVShockSignal TransductionSmall Interfering RNASurfaceT-LymphocyteTestingToxic effectTumor Necrosis Factor ReceptorVesicular stomatitis Indiana virusViral Load resultViral PhysiologyVirusVirus DiseasesVirus Replicationantiretroviral therapycell killingcytokinedisorder preventionexperienceexperimental studyexposed human populationkidney cellkillingsmemberpreventreceptorresponsetherapy resistanttranscriptome sequencing
中文摘要
摘要
英文摘要
Abstract
In searching for the protein mediating the innate CD8+ cell non-cytotoxic anti-HIV response (CNAR) we have
discovered that the external portion of CD137 (4-1BB) is a soluble protein that can induce a cellular antiviral
state that prevents HIV replication. The full-length membrane-bound CD137 does not trigger this activity. The
interaction of CD137 with its ligand, CD137L activates the cells expressing CD137, particularly T lymphocytes.
The role of sCD137 is not known. sCD137 inhibits replication of all HIV isolates tested as well as polio,
adenovirus, cytomegalovirus, and VSV. It is only active in human and primate cells and blocks virus replication
at the transcription level. sCD137 can be found naturally in the blood of some individuals. Timing experiments
have suggested that sCD137 can induce this antiviral state within a few hours after the exposure of human
cells. Pilot studies have indicated that CD137L antibodies block the induction of the antiviral state by sCD137.
Our hypothesis is that sCD137 interacts with the ligand CD137L on the cell surface to induce an intracellular
antiviral state. Our proposed studies are aimed at confirming this hypothesis through #1, Using RNA-Seq, to
determine the intracellular pathway responsible for the sCD137-induced antiviral state and #2, Using CRISPR-
Cas9, to confirm that the sCD137/CD137L interaction is involved in inducing the antiviral state. These studies
offer a new direction in antiviral immunotherapy that could be effective alone or in combination with
antiretroviral therapy. Soluble CD137 could also be effective in "shock and kill" cure strategies in which the
spread of the activated virus to uninfected cells could be controlled.
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会议论文
HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem Cells
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批准号:8659220
-
项目类别:
-
资助金额:$61.31万
-
财政年份:2014
-
负责人:JAY A LEVY
-
依托单位:
HIV Cure with CCr5 (-) Human IPS Hematopoietic Stem Cells
-
批准号:9052116
-
项目类别:
-
资助金额:$69.77万
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财政年份:2014
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负责人:JAY A LEVY
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依托单位:
HIV cure with CCR5 (-) human IPS hematopoietic stem cells
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批准号:8470397
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项目类别:
-
资助金额:$51.82万
-
财政年份:2012
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负责人:JAY A LEVY
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依托单位:
Protection from HIV Infection in Intravenous Drug Users
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批准号:8012878
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项目类别:
-
资助金额:$25.53万
-
财政年份:2010
-
负责人:JAY A LEVY
-
依托单位:
Protection from HIV Infection in Intravenous Drug Users
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批准号:8100171
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项目类别:
-
资助金额:$19.58万
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财政年份:2010
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
-
批准号:7894208
-
项目类别:
-
资助金额:$15.0万
-
财政年份:2009
-
负责人:JAY A LEVY
-
依托单位:
IDENTIFICATION OF CD8+ CELL ANTI HIV FACTOR
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批准号:7724166
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项目类别:
-
资助金额:$1.15万
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财政年份:2008
-
负责人:JAY A LEVY
-
依托单位:
IDENTIFICATION OF CD8+ CELL ANTI HIV FACTOR
-
批准号:7601815
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项目类别:
-
资助金额:$0.45万
-
财政年份:2007
-
负责人:JAY A LEVY
-
依托单位:
IDENTIFICATION OF CD8+ CELL ANTI HIV FACTOR
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批准号:7369044
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项目类别:
-
资助金额:$1.89万
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财政年份:2006
-
负责人:JAY A LEVY
-
依托单位:
IDENTIFICATION OF CD8+ CELL ANTI HIV FACTOR
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批准号:7180932
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项目类别:
-
资助金额:$2.7万
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财政年份:2005
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负责人:JAY A LEVY
-
依托单位:
IDENTIFICATION OF CD8+ CELL ANTI HIV FACTOR
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批准号:6976620
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项目类别:
-
资助金额:$3.89万
-
财政年份:2004
-
负责人:JAY A LEVY
-
依托单位:
Project 3 - MBSR & the Immune System in Early HIV Infection
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批准号:6884431
-
项目类别:
-
资助金额:$17.85万
-
财政年份:2004
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
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批准号:7496465
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项目类别:
-
资助金额:$54.28万
-
财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
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批准号:6837659
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项目类别:
-
资助金额:$63.98万
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财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
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批准号:6770071
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项目类别:
-
资助金额:$62.12万
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财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
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批准号:7787097
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项目类别:
-
资助金额:$72.15万
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财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
20Years of HIV Research: From Discovery to Understanding
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批准号:6571328
-
项目类别:
-
资助金额:$1.2万
-
财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
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批准号:7628613
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项目类别:
-
资助金额:$37.89万
-
财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
-
批准号:7338413
-
项目类别:
-
资助金额:$19.25万
-
财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
Role of Innate Immunity in Controlling HIV Infection
-
批准号:7338224
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项目类别:
-
资助金额:$23.07万
-
财政年份:2003
-
负责人:JAY A LEVY
-
依托单位:
海外基金