Proteomic profiling of oral epithelial-cells from HIV-positive and healthy subjects

With the advent of highly active anti-retroviral therapy (HAART), HIV infected individuals have renewed hope for durable remission. However, the incidence of certain oral manifestations, such as apthous ulcers, salivary gland disease and oral warts have either not changed or worsened. Objective: To determine if HIV and/or HAART alter the composition of oral epithelial cell derived proteins and their functional networks. Methods: The cell lysates from human oral epithelial cell (HOEC) monolayers of both healthy (n=4) and HIV positive subjects (n=4) were pooled and subjected to proteome analyses using 2D-DIGE techniques. Differentially expressed proteins were subjected to in-gel digestion and identified by tandem mass spectrometry (MS/MS). The identified proteins were analyzed for related biological function by ingenuity software (http://www.ingenuity.com/). Results: A total of 2,370 protein spots were detected. Spots that conformed to 1.5 fold changes with p values equal to or less than 0.05 in the HIV positive samples when compared to HIV negative samples were assigned as proteins of interest. Out of the 153 identified proteins of interest, 137 (~90%) were down-regulated and 16 were up-regulated in samples obtained from HIV positive subjects. Interestingly, the most abundantly down regulated proteins were associated with cell death (apoptosis) and immunological responses. Conclusion: Both cellular and innate immune mechanisms may be impaired in the oral mucosa as a result of HIV infection. Network analysis of all the impaired proteins is now being carried out, using comprehensive computational software to discover the biological pathways and networks involved in the HIV and/or HAART-induced perturbation of oral epithelial cell derived proteins. Supported by NIH/NIDCR R01DE016334, R01DE018276.