Tissue and Cell Reservoirs for HIV
HIV 的组织和细胞库
基本信息
- 批准号:6696231
- 负责人:
- 金额:$ 27.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-07-15 至 2007-12-31
- 项目状态:已结题
- 来源:
- 关键词:HIV infections biological transport biopsy bone marrow brain cerebrospinal fluid clinical research dendritic cells drug resistance flow cytometry helper T lymphocyte host organism interaction human subject immunocytochemistry latent virus infection leukocyte activation /transformation longitudinal human study lymph nodes macrophage molecular cloning monocyte neuropsychological tests nucleic acid sequence postmortem sample collection
项目摘要
DESCRIPTION (provided by applicant): Success in treating HIV/AIDS is critically dependent upon a thorough and accurate understanding of occult infection---where and how HIV persistence is maintained. This proposal focuses on the macrophage and follicular dendritic cell (FDC) as cellular reservoirs for HIV, and bone marrow and brain as tissue reservoirs. Although they have received comparatively little attention, these cell and tissue compartments most probably represent HIV reservoirs of considerable significance. Importantly, each appears capable of serving as a sanctuary for latent HIV infection. We propose here to determine if, indeed, these cells and tissues can serve as latently infected hosts able to yield infectious particles that can seed the body. We seek to identify patterns of HIV trafficking between lymphoid tissues and the Central Nervous System, and determine if the brain can reseed the periphery with HIV. We also seek to identify cell and tissue reservoirs for antiretroviral drug-sensitive, versus drug-resistant, HIV. For these studies, HIV genotyping will be performed using contemporaneously-collected ante-mortem bone marrow and excised cervical lymph node biopsy specimens, in conjunction with patient-matched plasma, cerebrospinal fluid (CSF), and separated blood monocyte and T-lymphocyte specimens collected concomitantly, as well as prior to, and following biopsy. Two regions of the HIV genome will be examined, the V1-V4 region of the envelope gene, and a 1.2kb fragment which includes the protease gene and that portion of the reverse transcriptase gene which codes for most of the antiretroviral resistance mutations of significance. To optimally address the question of whether the brain can seed the periphery with HIV, we will evaluate the HIV species present not only within the lymph node (LN) CD4+ T-cell population, but also those associated with LN germinal center follicular dendritic cells (FDC). These investigations will be complemented with studies of post-mortem tissues. In addition, we seek to identify events in bone marrow associated with systemic virologic failure. Attention will be paid to HIV expression and monocyte/macrophage activation in marrow. Immunohistochemistry and flow cytometry methods will be used. These studies will yield important new information regarding HIV reservoirs, as well as the contributions of events in bone marrow to HIV immunopathogenesis and disease progression.
描述(由申请人提供):治疗艾滋病毒/艾滋病的成功关键取决于对隐匿性感染的彻底和准确的理解-艾滋病毒在何处以及如何持续存在。该建议的重点是巨噬细胞和滤泡树突状细胞(FDC)作为HIV的细胞库,以及骨髓和大脑作为组织库。虽然它们受到的关注相对较少,但这些细胞和组织隔室最有可能代表具有相当重要意义的HIV储库。重要的是,每一种病毒似乎都能成为潜伏的艾滋病毒感染的避难所。我们在这里提出,以确定是否,确实,这些细胞和组织可以作为潜伏感染的主机能够产生感染性粒子,可以播种身体。我们试图识别淋巴组织和中枢神经系统之间的HIV运输模式,并确定大脑是否可以用HIV重新播种外周。我们还寻求确定抗逆转录病毒药物敏感的细胞和组织库,与耐药的艾滋病毒。对于这些研究,将使用同时采集的死前骨髓和切除的颈部淋巴结活检标本,以及同时、活检前后采集的患者匹配血浆、脑脊液(CSF)和分离的血液单核细胞和T淋巴细胞标本进行HIV基因分型。将检查HIV基因组的两个区域,包膜基因的V1-V4区域,以及包括蛋白酶基因和编码大多数重要抗逆转录病毒抗性突变的逆转录酶基因部分的1.2kb片段。为了最佳地解决大脑是否可以用HIV接种外周的问题,我们将评估不仅存在于淋巴结(LN)CD 4 + T细胞群中的HIV种类,而且还评估与LN生发中心滤泡树突状细胞(FDC)相关的HIV种类。这些调查将辅之以对死后组织的研究。此外,我们试图确定与全身病毒学失败相关的骨髓事件。将关注骨髓中的HIV表达和单核细胞/巨噬细胞活化。将使用免疫组织化学和流式细胞术方法。这些研究将产生关于HIV储库的重要新信息,以及骨髓中事件对HIV免疫发病机制和疾病进展的贡献。
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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SUZANNE GARTNER其他文献
SUZANNE GARTNER的其他文献
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{{ truncateString('SUZANNE GARTNER', 18)}}的其他基金
HIV Infection in Bone Marrow: A Reservoir for Viral Persistence
骨髓中的艾滋病毒感染:病毒持续存在的储存库
- 批准号:
8732072 - 财政年份:2014
- 资助金额:
$ 27.36万 - 项目类别:
HIV Infection in Bone Marrow: A Reservoir for Viral Persistence
骨髓中的艾滋病毒感染:病毒持续存在的储存库
- 批准号:
8797299 - 财政年份:2014
- 资助金额:
$ 27.36万 - 项目类别:
Viral/Cell Determinants of HIV Drug Resistance in CNS
CNS 中 HIV 耐药性的病毒/细胞决定因素
- 批准号:
6696203 - 财政年份:2003
- 资助金额:
$ 27.36万 - 项目类别:
Viral/Cell Determinants of HIV Drug Resistance in CNS
CNS 中 HIV 耐药性的病毒/细胞决定因素
- 批准号:
6883942 - 财政年份:2003
- 资助金额:
$ 27.36万 - 项目类别:
Viral/Cell Determinants of HIV Drug Resistance in CNS
CNS 中 HIV 耐药性的病毒/细胞决定因素
- 批准号:
7067993 - 财政年份:2003
- 资助金额:
$ 27.36万 - 项目类别:
Viral/Cell Determinants of HIV Drug Resistance in CNS
CNS 中 HIV 耐药性的病毒/细胞决定因素
- 批准号:
6772603 - 财政年份:2003
- 资助金额:
$ 27.36万 - 项目类别:
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