Identification, cloning, and in vitro characterization of transmitted/founder vir

传播/创始病毒的鉴定、克隆和体外表征

基本信息

  • 批准号:
    8497586
  • 负责人:
  • 金额:
    $ 38.58万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-07-01 至 2015-06-30
  • 项目状态:
    已结题

项目摘要

One of the most important knowledge gaps in HIV/SIV vaccine research relates to the biological properties of viruses that are responsible for mucosal transmission. Within this HIVRAD consortium, this project will address this priority area by taking advantage of our laboratory's recent discovery of a novel strategy for identifying mucosally transmitted HIV-1 and SIV viral genomes (Salazar et al., J Virol, 2008; Keele, PNAS, 2008; Salazar, J Exp Med, 2009; Keele, J Exp Med, 2009). This strategy, which is based on single genome amplification, sequencing and analysis of plasma viral RNA within the context of a model of random virus evolution, identifies those viruses that are actually responsible for transmission and productive infection. This innovation, in turn, makes possible for the first time the molecular cloning and biological characterization of such transmitted/founder virus genomes. In this project, we propose to extend this enabling technology to the SIV-macaque infection model to test the following hypothesis: Molecular clones of transmitted/founder SIVs will reveal the particular properties of cell tropism, receptor and co-receptor usage, and neutralization phenotype that are necessary and sufficient for successful transmission via intrarectal, intravaginal and intravenous infection routes. Specific aims include: 1. To identify and enumerate transmitted/founder viruses in Indian rhesus macaques following intrarectal, intravaginal and intravenous infection with new genetically diverse SIVsmm strains. To moleculariy clone full-length genomes of transmitted/founder viruses responsible for productive infection by intrarectal, intravaginal and intravenous routes. To determine the in vitro biological properties of molecular clone-derived transmitted/founder viruses. To prepare stocks of transmitted/founder viruses for in vivo testing in Indian rhesus macaques. Results from these studies will shed new light on the molecular mechanisms underiying mucosal HIV/SIV transmission, identify new targets for vaccine-elicited immune responses, and generate a much needed set of new genetically-diverse SIV challenge strains for transmission, pathogenesis and vaccine research.
HIV/SIV疫苗研究中最重要的知识差距之一与生物学特性有关。 负责粘膜传播的病毒的特性。在HIVRAD联盟中, 该项目将通过利用我们实验室最近发现的一种新的 鉴定粘膜传播HIV-1和SIV病毒基因组的策略(Salazar等,J Virol,2008; Keele,PNAS,2008; Salazar,J Exp Med,2009; Keele,J Exp Med,2009)。这一战略是基于 单基因组扩增,测序和分析血浆病毒RNA的背景下的模型, 随机病毒进化,识别那些实际负责传播和生产的病毒, 感染这一创新,反过来,使第一次有可能的分子克隆和生物 这类传播/创始病毒基因组的表征。在这个项目中,我们建议将其扩展到 使SIV-猕猴感染模型的技术能够测试以下假设: 传递/建立SIV将揭示细胞向性、受体和共受体使用的特定性质, 和中和表型,这些表型是通过直肠内成功传播所必需和充分的, 阴道内和静脉内感染途径。具体目标包括: 1.识别和计数印度恒河猴中的传播/创始病毒, 直肠内、阴道内和静脉内感染新的遗传多样性SIVsmm株。 为了分子克隆负责生产的传播/创始病毒的全长基因组, 经直肠、阴道和静脉途径感染。 确定分子克隆衍生的传播/创始病毒的体外生物学特性。 制备用于印度恒河猴体内试验的传播/创始病毒储备液。 这些研究结果将为粘膜HIV/SIV的分子机制提供新的线索 传播,确定疫苗引起的免疫反应的新靶点,并产生急需的一套 新的遗传多样性SIV攻击毒株的传播,致病和疫苗研究。

项目成果

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Beatrice H Hahn其他文献

Beatrice H Hahn的其他文献

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{{ truncateString('Beatrice H Hahn', 18)}}的其他基金

Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
优化聚糖屏蔽覆盖、种系 B 细胞受体结合和 V2-apex 靶向 HIV-1 Env 免疫原的表位多样性
  • 批准号:
    10686018
  • 财政年份:
    2019
  • 资助金额:
    $ 38.58万
  • 项目类别:
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
优化聚糖屏蔽覆盖、种系 B 细胞受体结合和 V2-apex 靶向 HIV-1 Env 免疫原的表位多样性
  • 批准号:
    10021396
  • 财政年份:
    2019
  • 资助金额:
    $ 38.58万
  • 项目类别:
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
优化聚糖屏蔽覆盖、种系 B 细胞受体结合和 V2-apex 靶向 HIV-1 Env 免疫原的表位多样性
  • 批准号:
    10241429
  • 财政年份:
    2019
  • 资助金额:
    $ 38.58万
  • 项目类别:
Optimizing glycan shield coverage, germline B cell receptor binding and epitope diversity of V2-apex targeted HIV-1 Env immunogens
优化聚糖屏蔽覆盖、种系 B 细胞受体结合和 V2-apex 靶向 HIV-1 Env 免疫原的表位多样性
  • 批准号:
    10468221
  • 财政年份:
    2019
  • 资助金额:
    $ 38.58万
  • 项目类别:
Virus and Antibody Gene Sequencing Core
病毒和抗体基因测序核心
  • 批准号:
    10370981
  • 财政年份:
    2017
  • 资助金额:
    $ 38.58万
  • 项目类别:
Virus and Antibody Gene Sequencing Core
病毒和抗体基因测序核心
  • 批准号:
    10117168
  • 财政年份:
    2017
  • 资助金额:
    $ 38.58万
  • 项目类别:
Virus and Antibody Gene Sequencing Core
病毒和抗体基因测序核心
  • 批准号:
    10631869
  • 财政年份:
    2017
  • 资助金额:
    $ 38.58万
  • 项目类别:
Studies of the precursor of the human AIDS virus in its natural chimpanzee host
对黑猩猩天然宿主中人类艾滋病病毒前体的研究
  • 批准号:
    9186500
  • 财政年份:
    2015
  • 资助金额:
    $ 38.58万
  • 项目类别:
Restriction of HIV-1 transmission by type 1 interferons
1 型干扰素限制 HIV-1 传播
  • 批准号:
    8786805
  • 财政年份:
    2014
  • 资助金额:
    $ 38.58万
  • 项目类别:
Restriction of HIV-1 transmission by type 1 interferons
1 型干扰素限制 HIV-1 传播
  • 批准号:
    9275913
  • 财政年份:
    2014
  • 资助金额:
    $ 38.58万
  • 项目类别:

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