Novel Approaches to Innate Immunity Against HIV-1 and Other Co-infection Viruses
针对 HIV-1 和其他混合感染病毒的先天免疫的新方法
基本信息
- 批准号:9882985
- 负责人:
- 金额:$ 77.75万
- 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
- 起止时间:2017-04-01 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AIDS/HIV problemAdaptive Immune SystemAddressAntiviral AgentsCell Culture TechniquesCell modelCellsDataDiseaseGoalsHIV-1HumanImmuneIndividualInflammatoryInnate Immune SystemLifeModelingMusNational Institute of Drug AbuseNatural ImmunityPathologyPopulations at RiskPrevention strategyProteomePublishingRNA VirusesRNA-Directed RNA PolymeraseRiskSolidTransgenic MiceTransgenic OrganismsVaccinesViral ProteinsVirus DiseasesVirus ReplicationWorkadaptive immunityaddictionantiviral immunitybaseco-infectioninnovationnovel strategiesoptimismpathogenresponseside effectviral RNA
项目摘要
Project Summary
Of the two main goals of the HIV-1 field – immune protection of the uninfected, and cure
– cure is more imaginable at present. Certainly a globally applicable sterilizing vaccine
seems far away. There is little optimism that currently available strategies will produce
effective adaptive immune system protection against HIV-1 for uninfected but at-risk
individuals (people with the disease of addiction, people with sexual exposure). This
NIDA Avant Garde project will align with RFA goals by pursuing a solidly innovative
direction that also differs strongly from our previous work. It concerns innate rather than
adaptive immunity, and it is based on our recently published body of data showing that
transgenic expression of a viral RNA-dependent RNA polymerase (RdRP), in the
absence of other viral proteins, and therefore unsequestered in the cell within viral
replication factories, can profoundly reconfigure mammalian innate antiviral immunity. It
dramatically upregulates many antiviral factors, and provides broad-spectrum antiviral
protection to mice. This response is strongly HIV-1-protective in corroborative human
cell models. We hypothesize that it may also have application to the co-infection
pathogens that afflict people with addiction. In the mouse, the radically altered innate
immune system proteome is stable life-long and, surprisingly, does not trigger any
inflammatory pathology. Along with the profound antiviral effects, this latter provocative
and counterintuitive observation has multiple downstream discovery opportunities. Here
we will determine the mechanisms involved and use the discoveries to formulate new
strategies to achieve protection against HIV-1 in at-risk populations.
项目摘要
HIV-1领域的两个主要目标--对未感染者的免疫保护和治愈
- 目前,治疗是可以想象的。当然,一种全球适用的消毒疫苗
似乎很遥远。目前可用的战略能否产生
有效的适应性免疫系统保护未感染但处于危险中的HIV-1
个人(患有成瘾疾病的人,有性接触的人)。这
NIDA Avant Garde项目将通过追求坚实的创新,
这一点也与我们之前的工作有很大不同。它关注的是先天的,而不是
适应性免疫,它是基于我们最近发表的数据显示,
病毒RNA依赖性RNA聚合酶(RdRP)的转基因表达,
不存在其他病毒蛋白,因此在病毒内的细胞中未被隔离。
复制工厂,可以深刻地重新配置哺乳动物先天抗病毒免疫。它
显着上调许多抗病毒因子,并提供广谱抗病毒
保护老鼠这种反应在确证的人类免疫缺陷病毒(HIV-1)中具有强烈的保护作用。
细胞模型我们假设它也可以应用于合并感染
感染成瘾者的病原体在小鼠中,
免疫系统蛋白质组是终身稳定的,令人惊讶的是,
炎症病理学沿着深刻的抗病毒作用,后者挑衅
并且反直觉观察具有多个下游发现机会。这里
我们将确定所涉及的机制,并利用这些发现制定新的
在高危人群中实现艾滋病毒-1保护的战略。
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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Eric M. Poeschla其他文献
809. Suppression of Human Pancreatic Cancer Growth by Lentiviral Vector-Mediated Gene Transfer of Pigment Epithelium Derived Factor (PEDF)
- DOI:
10.1016/j.ymthe.2006.08.894 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Pranay D. Khare;Nils Loewen;Eric M. Poeschla - 通讯作者:
Eric M. Poeschla
463. COX-2-Based Gene Therapy: Reduction of Intraocular Pressure in a Glaucoma Gene Therapy Animal Model with Lentiviral Vectors Expressing COX-2, a Prostaglandin Synthase, or a Prostaglandin Receptor
- DOI:
10.1016/j.ymthe.2006.08.532 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Roman A. Barraza;Eric M. Poeschla - 通讯作者:
Eric M. Poeschla
466. Comprehensive Analyses of Diverse Lentiviral and Retroviral Vectors for Post-Entry Restriction by TRIM5α and Implications for Gene Therapy
- DOI:
10.1016/j.ymthe.2006.08.535 - 发表时间:
2006-01-01 - 期刊:
- 影响因子:
- 作者:
Dyana T. Saenz;Eric M. Poeschla - 通讯作者:
Eric M. Poeschla
Eric M. Poeschla的其他文献
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{{ truncateString('Eric M. Poeschla', 18)}}的其他基金
Introducing restriction factors into the genome of an AIDS virus host species
将限制因子引入艾滋病病毒宿主物种的基因组中
- 批准号:
9025396 - 财政年份:2015
- 资助金额:
$ 77.75万 - 项目类别:
Introducing restriction factors into the genome of an AIDS virus host species
将限制因子引入艾滋病病毒宿主物种的基因组中
- 批准号:
8645612 - 财政年份:2012
- 资助金额:
$ 77.75万 - 项目类别:
Introducing restriction factors into the genome of an AIDS virus host species
将限制因子引入艾滋病病毒宿主物种的基因组中
- 批准号:
8464631 - 财政年份:2012
- 资助金额:
$ 77.75万 - 项目类别:
Introducing restriction factors into the genome of an AIDS virus host species
将限制因子引入艾滋病病毒宿主物种的基因组中
- 批准号:
8410610 - 财政年份:2012
- 资助金额:
$ 77.75万 - 项目类别:
Dependency Factors in HIV-1 Cytoplasmic-Nuclear Transit and Integration
HIV-1 细胞质-核转运和整合的依赖性因素
- 批准号:
8660758 - 财政年份:2008
- 资助金额:
$ 77.75万 - 项目类别:
Dependency Factors in HIV-1 Cytoplasmic-Nuclear Transit and Intgeration
HIV-1 细胞质-核转运和整合的依赖性因素
- 批准号:
9023761 - 财政年份:2008
- 资助金额:
$ 77.75万 - 项目类别:
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