THE MIRIAM HOSPITAL
The overall goal of this pilot project is to determine whether recent advances in proteonomics can be applied to HIV-1 transmission as evaluated among persons exposed to HIV who remain uninfected as compared to HIV infected individuals. As the HIV/AIDS epidemic continues to accelerate our efforts to develop an HIV vaccine and other biomedical preventionl modalities are limited by our lack of understanding of the mechanisms through which some persons are protected against HIV in spite of recurrent exposure. Cellular proteins contribute to the development of HIV infection, yet the role of proteins in the prevention of HIV acquisition has not been explored. It is possible that the expression of cellular receptors, membrane proteins and cytokines may differ between exposed individuals who resist HIV infection as compared to those who become infected with HIV. Identification of novel proteins, or clarification of the role know proteins play in protection against HIV could lead to better HIV vaccine development, topical microbicide applications, or cellular targets for antiretroviral use as an HIV prevention modality. Stable Isotope Labeling of Amino Acids in Cell culture (SILAC) is a technique recently introduced as a mass spectrometry based strategy to quantitatively interrogate the WHOLE proteome. We wish to apply to technique of SILAC to determine whether a study of the entire proteome of infected vs. exposed/uninfected can identify a proteonomic signature of resistance. Hypothesis: It will be feasibile to successfully apply the technique of SILAC to samples from HIV infected persons as compared to individuals with a history of HIV exposure who remain uninfected. Specific Aims are to: 1) Co-enroll 100 participants from an ongoing study into this project-specifically 50 indivuduals with high exposure to HIV who remain uninfected and 50 HIV infected individuals. 2) Apply SILAC and identify major differences beween the two sample sets 3) Generate specific hypotheses for novel or previously identified proteins that specifically play a role in HIV protection.