Genetic Risk of HIV Acquisition: Mechanisms of Resilience
感染艾滋病毒的遗传风险:恢复机制
基本信息
- 批准号:10077116
- 负责人:
- 金额:$ 25.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdoptionAffectAfricanAnti-Retroviral AgentsApplications GrantsBehavioralBindingBiologicalBiological FactorsCCR5 geneCD4 Positive T LymphocytesCellsCodeColorCommunitiesComplexComprehensionCountryDataDeveloped CountriesDiseaseDistalDrug usageEnvironmental ExposureEpidemicEpidemiologyExposure toGaysGene FrequencyGenesGeneticGenetic PolymorphismGenetic RiskGenetic TranscriptionGenetic studyGleanGrantHIVHIV InfectionsHIV-1HaitiHematologic AgentsHeritabilityHomozygoteImmune systemImmunologicsIn VitroIndividualInfectionInterventionLeadLesbian Gay Bisexual Transgender QueerLos AngelesMammalian CellMediatingMethodsModernizationMothersMutationNew YorkPharmaceutical PreparationsPharmacotherapyPhenotypePlayPopulationPopulation GeneticsPredispositionPreventionPrevention strategyProteinsResistance to infectionRiskRisk FactorsRoleRouteSepsisSexually Transmitted DiseasesSurfaceTestingUnsafe SexValidationVertical Disease TransmissionViralVirusWorkbaseblood productcase controlcausal variantcell typecohortcondomscytokinedrug abstinencegenetic analysisgenetic associationgenetic variantgenome wide association studygenome-widehigh riskhigh risk behaviorhigh risk populationimprovedinfection riskinflammatory markerintravenous administrationintravenous drug usemennovelpolygenic risk scorepre-exposure prophylaxisprematurepreventreceptorresiliencerisk variantsexsocial stigmastatisticstrait
项目摘要
PROJECT SUMMARY/ABSTRACT
This new R21 submission is entitled “Genetic Risk of HIV Acquisition: Mechanisms of Resilience”. Soon after
the identification of a new disease amongst gay men in Los Angeles and New York, originally called GRID,
epidemiological evidence suggested a sexually transmitted infection, which was then confirmed in populations
in Haiti and African identified with infection with HIV-1. In addition to infection through sex, intravenous
administration of contaminated blood products or drug use could lead to infection, as well as mother to child
transmission. Blood infection was identified as the highest risk, with different routes of sexual exposure
associated with different identifiable risks of infection. Before antiretroviral drug therapy became available,
around one third of babies born to infected mothers were infected, while two thirds were not. Thus, it appeared
that epidemiological and behavioral factors could predict HIV-1 susceptibility. However, individuals exposed to
HIV infection who had not became infected helped identify the defective Δ32 form of CCR5 receptor which
misfolded at the surface of a CD4+ cell and could not be infected, and in homozygote form, led to resistance to
infection with R5 using viruses. However, no genome-wide significant polymorphisms were found associated
with HIV-1 acquisition, which has led the field to move away from genetic association analyses. We were puzzled
from recent studies of sex workers exposed to HIV-1 who did not become infected despite high risk behavior
and wondered if genetic resilience to HIV-1 acquisition had been missed. Population genetic methods have
developed substantially in recent years, now allowing for powerful, biologically-informative analyses even in
moderately-sized gene wide association studies (GWAS). In preliminary data, we reanalyzed the largest GWAS
of HIV-1 acquisition and used gene-level enrichment analyses and polygenic risk scoring to identify novel genes
and inflammatory markers associated with acquisition risk. We have shown that HIV-1 acquisition is a surprisingly
heritable trait, and that certain cytokines are associated with HIV-1 resilience. These findings could lead to
potential new ways of preventing HIV-1 infection, including targeted interventions to those at highest risk. In this
grant, we will extend our analyses of the genetics of acquisition to validation cohorts including non-European
ancestry and determine mechanisms of immunological resilience. A better understanding of biological factors
influencing acquisition has the potential to develop our basic comprehension of HIV-1 acquisition, improve
prevention strategies and reduce social stigma.
项目总结/文摘
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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DOUGLAS F NIXON其他文献
DOUGLAS F NIXON的其他文献
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{{ truncateString('DOUGLAS F NIXON', 18)}}的其他基金
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转座元件在健康衰老和阿尔茨海默病中的作用
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$ 25.43万 - 项目类别:
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10398244 - 财政年份:2020
- 资助金额:
$ 25.43万 - 项目类别:
Development of Brain Organoids to Study the Impact of HIV-1, Drugs of Abuse and Aging on Cognitive Impairment
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- 批准号:
10063343 - 财政年份:2020
- 资助金额:
$ 25.43万 - 项目类别:
Development of Brain Organoids to Study the Impact of HIV-1, Drugs of Abuse and Aging on Cognitive Impairment
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- 资助金额:
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Genetic Risk of HIV Acquisition: Mechanisms of Resilience
感染艾滋病毒的遗传风险:恢复机制
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10251347 - 财政年份:2020
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