Exploring the features of HIV exceptional elite controllers in humanized mice

探索人源化小鼠中艾滋病毒杰出精英控制者的特征

基本信息

  • 批准号:
    10472752
  • 负责人:
  • 金额:
    $ 19.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-20 至 2024-07-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract: Newer insights into long-term natural control of HIV infection in the absence of ART will inform efforts to induce a functional cure or “remission.” Recent work has identified a subset of HIV elite controllers (EC) who are considered “exceptional” (EEC) with decades of virologic control without immunologic decline. Multiple mechanisms likely contribute to control in EECs, including a potent and sustained CD8+ T cell response. However, it is unclear whether EECs can maintain this status indefinitely, whether they have any ongoing viral activity and benefit from initiation of ART (or are harmed by withdrawal of ART), or whether they spontaneously cleared viral reservoirs. Whether such individuals may represent a true model of durable HIV control or, in some cases, a functional cure are important questions needing further investigation. Leveraging the largest elite controller cohort in the USA, the UCSF SCOPE cohort, our recent work focused on the question: is there a subset of ECs that might serve as a model for long-term ART-free HIV remission? Using the new intact proviral DNA assay (IPDA) to detect intact proviruses as well as sensitive antibody and T-cell immune-assays, we identified a small subset of 21 exceptional ECs with ultra-low reservoir size. Recent analyses using a combination of IPDA and FLIP-seq suggested that some ECs have ultralow levels of intact proviruses existing in a deeply latent state making their detection difficult. Therefore, novel virological assays to detect ultralow levels of latent HIV and immunological analyses to evaluate the role of CD8+ T cell control need to be employed to further our understanding of EECs. Towards this goal, we propose to employ our new ultrasensitive in vivo humanized mouse viral outgrowth assay (hmVOA) model for latent viral detection. This model also provides a unique in vivo setting to examine the role of immune control since CD4+ T cells from the EEC can be tested for viral outgrowth in the presence or absence of autologous CD8+ T cells believed to mediate control which is otherwise not possible to evaluate in a human setting. While full comprehension of EECs is a complex undertaking, here we propose to start with simpler initial goals to: 1. Determine whether intact HIV can be recovered (via viral outgrowth) from exceptional elite controllers not currently on ART and elite controllers on long-term ART using the humanized mouse viral outgrowth (hmVOA) assay 2. Ascertain if the predominant viral control in EEC is indeed mediated by CD8+ T cells and assess if this control can also provide resistance to a potential new HIV exposure (superinfection) in vivo. Results from here will help in furthering our understanding of the latent virus and the role of strong cell-mediated virus control in EECs.
项目总结/文摘:

项目成果

期刊论文数量(0)
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Ramesh Akkina其他文献

Ramesh Akkina的其他文献

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{{ truncateString('Ramesh Akkina', 18)}}的其他基金

A dual-purpose hu-mouse model for evaluating SIV and HIV cure strategies
用于评估 SIV 和 HIV 治疗策略的双用途人鼠模型
  • 批准号:
    10652685
  • 财政年份:
    2022
  • 资助金额:
    $ 19.34万
  • 项目类别:
Exploring the features of HIV exceptional elite controllers in humanized mice
探索人源化小鼠中艾滋病毒杰出精英控制者的特征
  • 批准号:
    10326905
  • 财政年份:
    2021
  • 资助金额:
    $ 19.34万
  • 项目类别:
Modeling the molecular evolution of SIV to HIV using humanized mice
使用人源化小鼠模拟 SIV 到 HIV 的分子进化
  • 批准号:
    9979747
  • 财政年份:
    2016
  • 资助金额:
    $ 19.34万
  • 项目类别:
Modeling the molecular evolution of SIV to HIV using humanized mice
使用人源化小鼠模拟 SIV 到 HIV 的分子进化
  • 批准号:
    9209297
  • 财政年份:
    2016
  • 资助金额:
    $ 19.34万
  • 项目类别:
An Ultrasensitive In Vivo Latent HIV Viral Outgrowth Assay Using Humanized Mice
使用人源化小鼠进行超灵敏体内潜伏 HIV 病毒生长测定
  • 批准号:
    9277371
  • 财政年份:
    2015
  • 资助金额:
    $ 19.34万
  • 项目类别:
An Ultrasensitive In Vivo Latent HIV Viral Outgrowth Assay Using Humanized Mice
使用人源化小鼠进行超灵敏体内潜伏 HIV 病毒生长测定
  • 批准号:
    8966520
  • 财政年份:
    2015
  • 资助金额:
    $ 19.34万
  • 项目类别:
Efficacy Testing of HIV-Specific Microbicides in Humanized Mice
HIV特异性杀微生物剂在人源化小鼠中的功效测试
  • 批准号:
    8410283
  • 财政年份:
    2012
  • 资助金额:
    $ 19.34万
  • 项目类别:
Modeling Next Generation HIV PrEP in Humanized Mice
在人源化小鼠中模拟下一代 HIV PrEP
  • 批准号:
    8330552
  • 财政年份:
    2012
  • 资助金额:
    $ 19.34万
  • 项目类别:
Modeling Next Generation HIV PrEP in Humanized Mice
在人源化小鼠中模拟下一代 HIV PrEP
  • 批准号:
    8662692
  • 财政年份:
    2012
  • 资助金额:
    $ 19.34万
  • 项目类别:
Modeling Next Generation HIV PrEP in Humanized Mice
在人源化小鼠中模拟下一代 HIV PrEP
  • 批准号:
    8478040
  • 财政年份:
    2012
  • 资助金额:
    $ 19.34万
  • 项目类别:

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