Functional Genomic Analysis of HIV-1 Infection in LTs

LT 中 HIV-1 感染的功能基因组分析

• 批准号: 6832863
• 负责人: ASHLEY T. HAASE
• 金额: $ 60.89万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-15 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832863
• 关键词: AIDS therapy; HIV infections; antiAIDS agent; biopsy; biotechnology; clinical research; cytotoxic T lymphocyte; functional /structural genomics; gene expression; gene expression profiling; helper T lymphocyte; human immunodeficiency virus 1; human subject; immunocytochemistry; immunogenetics; in situ hybridization; lymph nodes; lymphatic tissue; medical records; microarray technology; virus cytopathogenic effect; virus replication

DESCRIPTION (provided by applicant): Lymphatic tissues are the major site of HIV-1 replication, persistence and pathology prior to anti-retroviral treatment. After treatment suppresses viral replication, the pathological changes can be reversed to a variable extent. With the objective of identifying molecular bases for the pathological and reparative processes in HIV-1 infected lymphatic tissues, a preliminary microarray study was undertaken of gene expression in lymph node biopsies from HIV-1 infected patients before and after treatment. The study revealed a set of treatment-responsive genes related to host defenses, inflammatory pathology, and tissue repair. The overall objective of the proposed studies is to extend the gene profiling studies to gain further insight into the pathogenesis of HIV-1 infection in lymphatic tissues and the response to treatment that will translate into optimal timing and effectiveness of treatment. To this end, in specific aim 1 larger numbers of patients at different stages of HIV-1 infection will undergo lymph node biopsies for microarray analysis prior to and after antiretroviral treatment. In specific aim 2, in situ hybridization, immunohistochemical staining and quantitative image analysis will be used to link changes in gene expression to cells and anatomic sites and structures. Collectively, insights into pathological and reparative processes could lead to new approaches to decreasing the pathological consequences of infection and to new therapeutic strategies to enhance immune reconstitution.

描述（由申请方提供）：淋巴组织是抗逆转录病毒治疗前HIV-1复制、持续存在和病理学的主要部位。在治疗抑制病毒复制后，病理变化可以在不同程度上逆转。为了鉴定HIV-1感染淋巴组织中病理和修复过程的分子基础，对治疗前后HIV-1感染患者淋巴结活检中的基因表达进行了初步的微阵列研究。这项研究揭示了一组与宿主防御、炎症病理和组织修复相关的治疗反应基因。拟议研究的总体目标是扩展基因图谱研究，以进一步了解淋巴组织中HIV-1感染的发病机制以及对治疗的反应，从而转化为最佳治疗时机和有效性。为此，在具体目标1中，在抗逆转录病毒治疗之前和之后，将对处于HIV-1感染的不同阶段的大量患者进行淋巴结活检以进行微阵列分析。在具体目标2中，原位杂交、免疫组织化学染色和定量图像分析将用于将基因表达的变化与细胞和解剖部位和结构联系起来。总的来说，对病理和修复过程的了解可能会导致新的方法来减少感染的病理后果和新的治疗策略，以加强免疫重建。