PROTEIN PROFILING OF ORAL MUCOSA OF HIV TRANSGENIC MICE

描述（由申请人提供）：本研究计划的主要目的是利用蛋白质组学方法在艾滋病小鼠模型CD4C/HIV Tg小鼠中了解与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未成熟和CD4 CD8~成熟T细胞和树突状/巨噬细胞谱系细胞。这些Tg小鼠患上了一种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小鼠的口腔黏膜对口腔念珠菌病表现出增强的易感性，并允许慢性携带白色念珠菌，这是一种模仿艾滋病患者念珠菌病的病理。由于这些病理口腔表现与许多其他表型相关，与感染HIV-1的人类非常相似，我们假设这些Tg小鼠与人类艾滋病有关，并且它们构成了与人类HIV-1相关的口腔并发症的非常好的模型。

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.