PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE

HIV 转基因小鼠口腔粘膜的蛋白质分析

• 批准号: 7198094
• 负责人: Paul Jolicoeur
• 金额: $ 26.22万
• 依托单位: CLINICAL RESEARCH INSTITUTE OF MONTREAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7198094
• 关键词: Acquired Immunodeficiency Syndrome; CD4 Positive T Lymphocytes; Candida albicans; Candidiasis; Cells; Chronic; Defect; Dendritic Cells; Development; Disease; Environment; Epithelial Cells; Frequencies; HIV; HIV Infections; HIV-1; Heart; Human; Immune; Individual; Infection; Kidney; Lung diseases; Mature T-Lymphocyte; Mediating; Modeling; Mucous Membrane; Mus; Oral; Oral Manifestations; Oral candidiasis; Oral mucous membrane structure; Organ; Pathogenesis; Pathology; Peptides; Phenotype; Predisposition; Proteins; Proteomics; Public Health; Research; Research Proposals; Saliva; Transgenes; Transgenic Mice; age related; cell type; macrophage

DESCRIPTION (provided by applicant): The main objective of this research proposal is to understand the pathogenesis of oral complications associated with HIV infection, using a proteomic approach in a murine model of AIDS, the CD4C/HIV Tg mice. These Tg mice express some of the gene products of HIV-1 in cells normally targeted by HIV-1 infection in humans, namely CD4 CDS immature and CD4 CD8~ mature T cells and cells of the dendritic/macrophage lineage. These Tg mice develop an AIDS-like disease which is very similar to human AIDS, including immune defects and specific organ diseases (lung, heart and kidney). In particular, the oral mucosa of these Tg mice show enhanced susceptibility to oral candidiasis and allow chronic carriage of C. albicans, a pathology mimicking candidiasis described in individuals with AIDS. Because these pathological oral manifestations are associated with many other phenotypes very similar to those found in humans infected with HIV-1, we postulate that these Tg mice are relevant to human AIDS and that they constitute a very good model for the oral complications associated with HIV-1 in humans. In order to understand the pathogenesis of the oral mucosal changes favoring the development of candidiasis, we intend to use a proteomic approach on Tg oral mucosal tissues. In particular, we intend: Aim 1-To identify the major changes in protein profiles of saliva from CD4C/HIV Tg mice. Aim 2-To identify the major changes in protein profiles of total extracts of oral mucosal cells from CD4C/HIVTgmice. Aim 3-To generate sub-proteomic profiles of oral mucosal epithelial cells of CD4C/HIV Tg mice. Aim 4-To determine, using an inducible HIV transgene, whether changes in oral mucosal proteins induced by HIV expression are age-related. Aim 5-To identify the specific Nef-expressing cells of CD4C/HIV Tg mice associated with specific changes in protein profiles of oral mucosa. This research is especially relevant to public health in view of the high frequency of oral complications (especially candidiasis) in HIV-1 infected individuals.

描述（由申请人提供）：本研究计划的主要目的是在艾滋病小鼠模型（CD4C/HIV Tg 小鼠）中使用蛋白质组学方法，了解与 HIV 感染相关的口腔并发症的发病机制。这些Tg小鼠在人类HIV-1感染通常靶向的细胞中表达HIV-1的一些基因产物，即CD4 CDS未成熟T细胞和CD4 CD8~成熟T细胞以及树突/巨噬细胞谱系的细胞。这些Tg小鼠会患上与人类艾滋病非常相似的艾滋病样疾病，包括免疫缺陷和特定器官疾病（肺、心脏和肾脏）。特别是，这些 Tg 小鼠的口腔粘膜对口腔念珠菌病的敏感性增强，并允许长期携带白色念珠菌，这是一种与艾滋病患者中描述的念珠菌病相似的病理学。由于这些病理性口腔表现与许多其他表型相关，这些表型与感染 HIV-1 的人类中发现的表型非常相似，因此我们假设这些 Tg 小鼠与人类艾滋病有关，并且它们构成了人类与 HIV-1 相关的口腔并发症的非常好的模型。 为了了解有利于念珠菌病发展的口腔粘膜变化的发病机制，我们打算对 Tg 口腔粘膜组织使用蛋白质组学方法。特别是，我们打算： 目标 1 - 确定 CD4C/HIV Tg 小鼠唾液蛋白质谱的主要变化。目标 2-确定 CD4C/HIVTg 小鼠口腔粘膜细胞总提取物蛋白质谱的主要变化。目标 3-生成 CD4C/HIV Tg 小鼠口腔粘膜上皮细胞的亚蛋白质组谱。目标 4-使用诱导型 HIV 转基因确定 HIV 表达诱导的口腔粘膜蛋白变化是否与年龄相关。目标 5-鉴定与口腔粘膜蛋白质谱特定变化相关的 CD4C/HIV Tg 小鼠的特定 Nef 表达细胞。 鉴于 HIV-1 感染者口腔并发症（尤其是念珠菌病）的发生率很高，这项研究与公共卫生尤其相关。