The Proteomic and Functional Profile of HIV Positive Saliva

唾液是口腔健康的重要决定因素，含有大量蛋白质和多肽 使口腔保持良好的工作状态。唾液的一个显著特点是它有很强的抗菌力。 对多种入侵病原体的活性，如人类免疫缺陷病毒I型(HIV-1)， 真菌包括白色念珠菌，以及与口腔和全身疾病有关的大量细菌。 然而，关于唾液中存在的全部蛋白质种类及其变化模式，我们知之甚少。 在HIV-1感染过程中，很大程度上是由于传统的 技巧。本申请的目标是适应最先进的基于蛋白质组的技术， 蛋白质芯片和多维蛋白质识别层析(MudPIT)技术， 确定HIV阴性和HIV阳性个体唾液蛋白图谱的差异 在高活性抗逆转录病毒治疗(HAART)后。我们还提出了唾液蛋白的特征 HIV-1感染中特定生物标志物的异构体、结构修饰和浓度的变化 并建立关系数据库，对这些数据进行存储和统计分析。中环 该项目的假设是，在艾滋病毒感染过程中，唾液蛋白的图谱将发生改变，并将 HAART后恢复到正常水平。我们目前蛋白质组学方法的独特之处在于 集成了表面增强激光解吸/电离(SELDI)技术和MudPIT。它可以 同时比较几天内多个样本的蛋白质表达谱 ，从而提供了有史以来最全面、最灵敏的概览 正常人和疾病患者唾液中蛋白质组成和数量变化的研究进展 设置。我们坚信，这个项目的成果将对我们的 了解唾液对HIV-1感染的反应并促进新型抗逆转录病毒的鉴定 用作HIV-1感染的新型诊断、口服杀菌剂或治疗药物的因子。

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.