Saliva is an important determinant of oral health and contains a large number of proteins and peptidesthat keep oral cavity in good working order. One remarkable feature of saliva is its potent antimicrobialactivity 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 patternover the course of HIV-1 infection, largely due to the insensitivity and limited reproducibility of traditionaltechniques. 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, todetermine differences in salivary protein profiles in HIV-negative and HIV-positive individuals beforeand after high actively antiretroviral therapy (HAART). We also propose to characterize salivary proteinisoforms, structural modifications, and concentrations of selected biomarkers altered in HIV-1 infectionand to establish a relational database for storage and statistical analysis of these data. The centralhypothesis of this project is that the profile of salivary proteins will be altered in HIV infection and willrestore toward normal levels after HAART. The uniqueness of our current proteomic approach is theintegration of a surface-enhanced laser desorption/ionization (SELDI) technology and MudPIT. It cansimultaneously compare protein expression profiles from multiple samples within days at the sensitivityof femtogram level, thereby offering the most comprehensive overview with the greatest sensitivity everachieved as to the changes in identity and quantity of proteins in saliva samples in normal and diseasesettings. We strongly believe that results from this project will contribute significantly towards ourunderstanding of the salivary response to HIV-1 infection and facilitate identification of novel antiretroviralfactors for use as novel diagnostic, oral microbicides or therapeutics against HIV-1 infection.
Showing the most recent 10 out of 24 publications
