Host genetic determinants of HIV-AIDS susceptibility in a VA cohort
VA 队列中 HIV-AIDS 易感性的宿主遗传决定因素
基本信息
- 批准号:7908824
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-10-01 至 2014-09-30
- 项目状态:已结题
- 来源:
- 关键词:17q12AIDS/HIV problemAccountingAcquired Immunodeficiency SyndromeAddressAdultAffectAfrican AmericanAgeAgingAir Force PersonnelAlcohol consumptionAlcoholsAllelesAnti-Retroviral AgentsAntigen ReceptorsAntiviral AgentsAscaridilAwardBehaviorBindingBlood PlateletsCCL3L1 geneCCR5 geneCD209 geneCD4 Positive T LymphocytesCandidate Disease GeneCaringCell Adhesion MoleculesCell CountCellsCellular ImmunityCessation of lifeChemokine (C-C Motif) Receptor 5ChromosomesClinicalCodeCohort StudiesCommitComorbidityComplementComplexConsentCopy Number PolymorphismCost SharingDNADataData AnalysesDefensinsDependenceDependencyDipeptidyl-Peptidase IVDisciplineDiseaseDisease ProgressionDrug usageEnrollmentEpidemicEpidemiologic StudiesEpidemiologistEpidemiologyEquilibriumErythrocytesEvaluationEventEvolutionEyeFCGR3B geneFailureFamilyFc ReceptorFundingFunding AgencyGNB3 geneGTP-Binding ProteinsGap JunctionsGenerationsGenesGeneticGenetic DeterminismGenetic EpistasisGenetic VariationGenotypeGoalsGrantHIVHIV InfectionsHIV SeropositivityHIV-1HLA-B AntigensHLA-C AntigensHepatitis B VirusHepatitis C virusHighly Active Antiretroviral TherapyHispanic AmericansImmuneImmune responseImmunologicsImmunologistImmunologyIn VitroIndividualInfectionIntegration Host FactorsInterferonsInterleukin-12Interleukin-2Interleukin-7Intrinsic factorInvestigationJusticeKnowledgeLeadLearningLevel of EvidenceLifeLife Cycle StagesLigandsLiver diseasesMannose Binding LectinMannose-Binding LectinsManuscriptsMediatingMedical centerMessenger RNAMicrobeMutationN-terminalNational Institute on Alcohol Abuse and AlcoholismNatural HistoryNatureObservational StudyOutcomePathogenesisPathway interactionsPatientsPerinatalPhenotypePlayPopulationPredispositionPrevalenceProcessProductionPublic HealthRNA InterferenceRecoveryRelative (related person)ResearchResearch DesignResearch InfrastructureResourcesRiskRoleScienceScientistSerine ProteaseServicesSignal TransductionSiteSourceSpecimenSurfaceSystemT-LymphocyteTSG101 geneTestingTimeTranscriptTransducersTranslatingUnited States National Institutes of HealthUniversitiesVaccinesValidationVariantVeteransVial deviceViralViral Load resultWorkantiretroviral therapyapolipoprotein E-4basebench to bedsidebiobankchemokinechemokine receptorclinical careclinically relevantcohortcytokineexperiencegene interactiongenetic variantgenome wide association studygenome-widehuman diseaseimprovedin vivoindexinginnovationinsightinterestmedical schoolsmembermultidisciplinarynovelpromoterprotective effectpublic health relevanceracial and ethnicreceptorrepositoryresponseskillssuccesstherapy developmenttooltranscription factortranslational studytransmission processvaccine efficacy
项目摘要
DESCRIPTION (provided by applicant):
There is growing evidence that the host genetic make-up of an individual is a strong determinant of HIV/AIDS susceptibility during untreated HIV infection and immune recovery during highly active antiretroviral therapy (HAART). We will use state-of-the-art powerful genetic and statistical tools and targeted candidate gene approaches to identify genetic factors that influence HIV-AIDS susceptibility as well as immune recovery during highly active antiretroviral therapy (HAART) in a large cohort of adults from the VA, namely VA Aging Cohort Study (VACS). These studies will thus (a) uncover complex host gene-gene interactions that influence HIV-1 pathogenesis and immune recovery during HAART in vivo; (b) determine the relative contribution to these determinants to the HIV-1 epidemic at the population level; (c) translate these findings to real life practical issues such as improved clinical care of patients via genetic-based prognostication of AIDS as well as immune recovery during HAART; and (d) the influence of alcohol and age in immune depletion/recovery. In the current application we will test the overall hypothesis that (I) expression of members of the CD4 - CD4 ligand - CCR5 - CCR5 ligand nexus, including relevant transducers of coreceptor signals, will alter HIV/AIDS susceptibility and immune recovery during HAART (aim #1); (II) expression of and interaction between selected candidate genes that influence innate and adaptive immune responses will alter HIV-AIDS susceptibility and immune recovery during HAART (aim #2). These include genes (i) at the MHC and KIR locus; (ii) encoding cellular intrinsic factors (TRIM5 and Apobec3 family); (iii) involved in the HIV life cycle such as PPIA and TSG101; (iv) identified as HIV dependency factors (HDF), and (iv) Copy Number Variation (CNV) at the chemokine gene-rich locus on chromosome 17q12, complement components (C4A and C4B), Fc receptors (FCGR3), and defensins. Thus, this proposal seeks approval for the use of specimens at VA Central biorepository to support a collaborative study to explore the genetic mechanisms underlying HIV/AIDS susceptibility and immune recovery during HAART by amalgamating the unique skills and resources of the research teams at the VA Center for AIDS and HIV Infection at San Antonio, TX (PI: Dr Ahuja) and Yale University School of Medicine, New Haven, CT (PI: Dr Justice).
PUBLIC HEALTH RELEVANCE:
The studies proposed will provide new insights into the host factors that influence susceptibility to HIV and AIDS, and these findings could provide new ways to develop therapies and vaccines.
描述(由申请人提供):
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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Sunil K Ahuja其他文献
Sunil K Ahuja的其他文献
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{{ truncateString('Sunil K Ahuja', 18)}}的其他基金
Mechanistic clinical trial of blocking the IL-4/13 axis in asthmatics precision phenotyped in an aeroallergen challenge chamber before, during and after receipt of dupilumab
在接受 dupilumab 之前、期间和之后在空气过敏原激发室中精确表型的哮喘患者中阻断 IL-4/13 轴的机制临床试验
- 批准号:
10686198 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Mechanistic clinical trial of blocking the IL-4/13 axis in asthmatics precision phenotyped in an aeroallergen challenge chamber before, during and after receipt of dupilumab
在接受 dupilumab 之前、期间和之后在空气过敏原激发室中精确表型的哮喘患者中阻断 IL-4/13 轴的机制临床试验
- 批准号:
10488483 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Host genetic determinants of HIV-AIDS susceptibility in a VA cohort
VA 队列中 HIV-AIDS 易感性的宿主遗传决定因素
- 批准号:
8597354 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Host genetic determinants of HIV-AIDS susceptibility in a VA cohort
VA 队列中 HIV-AIDS 易感性的宿主遗传决定因素
- 批准号:
8391570 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Host genetic determinants of HIV-AIDS susceptibility in a VA cohort
VA 队列中 HIV-AIDS 易感性的宿主遗传决定因素
- 批准号:
7797897 - 财政年份:2009
- 资助金额:
-- - 项目类别: