The Proteomic and Functional Profile of HIV Positive Saliva

唾液是口腔健康的重要决定因素，含有大量的蛋白质和多肽 保持口腔正常工作唾液的一个显著特征是它的强效抗菌剂 抗多种入侵病原体如人免疫缺陷病毒I型（HIV-1）的活性， 真菌白色念珠菌，以及大量与口腔和全身性疾病相关的细菌。 然而，关于唾液中存在的总体蛋白质种类及其变化模式知之甚少 在HIV-1感染的过程中，主要是由于传统的检测方法的不敏感性和有限的重现性， 技术.本申请的目标是采用最先进的基于蛋白质组学的技术， 蛋白质芯片和多维蛋白质鉴定色谱（MudPIT）技术， 确定HIV阴性和HIV阳性个体的唾液蛋白谱差异， 高活性抗逆转录病毒治疗（HAART）后。我们还建议表征唾液蛋白 HIV-1感染中改变的同种型、结构修饰和选定生物标志物的浓度 并建立一个关系数据库，用于存储和统计分析这些数据。中央 该项目的假设是，唾液蛋白的分布将在HIV感染中改变， HAART后恢复正常水平。我们目前的蛋白质组学方法的独特之处在于， 表面增强激光解吸/电离（SELDI）技术和MudPIT的集成。它可以 在几天内同时比较多个样本的蛋白表达谱， 从而提供有史以来最全面的概述和最高的灵敏度 在正常和疾病的唾液样品中， 设置.我们坚信，该项目的成果将大大有助于我们的 了解唾液对HIV-1感染的反应，并促进新型抗逆转录病毒药物的鉴定 用作抗HIV-1感染的新型诊断、口服杀微生物剂或治疗剂的因子。

Saliva is an important determinant of oral health and contains a large number of proteins and peptides that keep oral cavity in good working order. One remarkable feature of saliva is its potent antimicrobial activity against a wide array of invading pathogens such as human immunodeficiency virus type I (HIV-1), the fungus Candida albicans, and a large number of bacteria associated with oral and systemic diseases. However, little is known regarding the overall protein species present in saliva and its changing pattern over the course of HIV-1 infection, largely due to the insensitivity and limited reproducibility of traditional techniques. It is the goal of this application to adapt the state-of-the-art proteomic-based technique, ProteinChip and multidimensional protein identification chromatography (MudPIT) technologies, to determine differences in salivary protein profiles in HIV-negative and HIV-positive individuals before and after high actively antiretroviral therapy (HAART). We also propose to characterize salivary protein isoforms, structural modifications, and concentrations of selected biomarkers altered in HIV-1 infection and to establish a relational database for storage and statistical analysis of these data. The central hypothesis of this project is that the profile of salivary proteins will be altered in HIV infection and will restore toward normal levels after HAART. The uniqueness of our current proteomic approach is the integration of a surface-enhanced laser desorption/ionization (SELDI) technology and MudPIT. It can simultaneously compare protein expression profiles from multiple samples within days at the sensitivity of femtogram level, thereby offering the most comprehensive overview with the greatest sensitivity ever achieved as to the changes in identity and quantity of proteins in saliva samples in normal and disease settings. We strongly believe that results from this project will contribute significantly towards our understanding of the salivary response to HIV-1 infection and facilitate identification of novel antiretroviral factors for use as novel diagnostic, oral microbicides or therapeutics against HIV-1 infection.