Mechanistic Studies of HIV-exposed Seronegative Individuals

HIV 血清阴性个体的机制研究

基本信息

  • 批准号:
    8503631
  • 负责人:
  • 金额:
    $ 36.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-08-01 至 2014-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): As detailed in the "Request For Applications" to which this proposal responds, the mechanisms of resistance of some individuals to HIV-1 infection (highly exposed seronegative, HESN) remain poorly understood. Major questions regarding this phenomenon were raised at an NIH workshop on this topic that serves as the basis for this RFA, including: 1) What is different in HESN versus those who get infected? 2) What is the immune response in HESN and is it just a marker of exposure or a correlate of protection? 3) What are the HESN host factors that help HESN resist infection? This proposal addresses these issues by exploring the overarching hypothesis that innate immune reactivity is a key determinant of CD4+ T lymphocyte activation at mucosal surfaces, and therefore a key determinant of susceptibility to HIV-1 infection of an individual. HESN may be different in terms of innate immune reactivity, which would be a key difference in the immune response of these persons compared to the general population, and not necessarily HIV-1-specific. The host factors determining this difference likely would be genetic, which will be explored by whole genome single nucleotide polymorphism examination in a complementary study. We will pursue this hypothesis by examining a unique cohort of men in the Multicenter AIDS Cohort Study who had extremely high-risk sexual exposures in the early- to mid-1980s, yet remained uninfected. The susceptibility and reactivity of their mucosal innate immune system will be assessed using HIV-1 infection and examining the effects of defined stimuli of pattern recognition receptors. We will focus on their site of sexual exposure, the rectal mucosa. Specifically, we propose: ¿ To determine innate immune signals important for HIV-1 replication in gut mucosa and quantitate the ability of gut mucosa from HESN to support HIV-1 replication ¿ To assess the innate immune responsiveness of HESN gut mucosa to different stimuli ¿ To examine the phenotypes of antigen-presenting cells in the gut mucosa of HESN
描述(由申请人提供):正如本提案所回应的“申请请求”中所详述的,对某些个体对HIV-1感染(高度暴露血清阴性,HESN)的耐药机制仍知之甚少。关于这一现象的主要问题是在美国国立卫生研究院关于这一主题的研讨会上提出的,该研讨会作为RFA的基础,包括:1)HESN与感染者有什么不同?2)HESN中的免疫反应是什么?它只是暴露的标志物还是保护的相关物?3)什么是HESN的宿主因子,帮助HESN抵抗感染?该提案通过探索先天免疫反应性是粘膜表面CD 4 + T淋巴细胞活化的关键决定因素,因此是个体对HIV-1感染易感性的关键决定因素的总体假设来解决这些问题。HESN可能在先天免疫反应性方面不同,这将是这些人与普通人群相比免疫反应的关键差异,并且不一定是HIV-1特异性的。决定这种差异的宿主因素可能是遗传性的,这将在一项补充研究中通过全基因组单核苷酸多态性检测来探索。我们将通过研究多中心艾滋病队列研究中的一个独特的男性队列来探讨这一假设,这些男性在20世纪80年代早期至中期有极高风险的性暴露,但仍然没有感染。将使用HIV-1感染并检查模式识别受体的限定刺激的影响来评估其粘膜先天免疫系统的易感性和反应性。我们将重点关注他们的性暴露部位,直肠粘膜。具体而言,我们建议:¿确定肠粘膜中对HIV-1复制重要的先天免疫信号,并定量HESN肠粘膜支持HIV-1复制的能力;评估HESN肠粘膜对不同刺激的先天免疫应答;检查HESN肠粘膜中抗原呈递细胞的表型。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Peter A Anton其他文献

The Other Compartment: Challenges and Progress in Rectal Microbicide Development
  • DOI:
    10.1186/1742-4690-2-s1-s89
  • 发表时间:
    2005-12-08
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Peter A Anton
  • 通讯作者:
    Peter A Anton

Peter A Anton的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Peter A Anton', 18)}}的其他基金

Topical Microbicides: Targeted Intracellular Delivery
局部杀菌剂:靶向细胞内递送
  • 批准号:
    8810224
  • 财政年份:
    2014
  • 资助金额:
    $ 36.17万
  • 项目类别:
Topical Microbicides: Targeted Intracellular Delivery
局部杀菌剂:靶向细胞内递送
  • 批准号:
    8711813
  • 财政年份:
    2014
  • 资助金额:
    $ 36.17万
  • 项目类别:
Data management and biostatistics
数据管理和生物统计学
  • 批准号:
    7979343
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
Exploratory human trials of rectal microbicides
直肠杀菌剂的探索性人体试验
  • 批准号:
    7979345
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
Administrative
行政的
  • 批准号:
    7979338
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
Regulatory compliance and human subjects safety
法规遵从性和人体受试者安全
  • 批准号:
    7979340
  • 财政年份:
    2009
  • 资助金额:
    $ 36.17万
  • 项目类别:
Mucosal Immunology Core
粘膜免疫学核心
  • 批准号:
    7480739
  • 财政年份:
    2008
  • 资助金额:
    $ 36.17万
  • 项目类别:
Core A - Administrative
核心 A - 行政
  • 批准号:
    7127921
  • 财政年份:
    2006
  • 资助金额:
    $ 36.17万
  • 项目类别:
Microbicide Development Program (MDP)
杀菌剂开发计划 (MDP)
  • 批准号:
    7278576
  • 财政年份:
    2004
  • 资助金额:
    $ 36.17万
  • 项目类别:
Microbicide Development Program (MDP)
杀菌剂开发计划 (MDP)
  • 批准号:
    7107173
  • 财政年份:
    2004
  • 资助金额:
    $ 36.17万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 36.17万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了