Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities

This is the first comparative study that used SMPP, a step-wise proteomic protocol that employed both SpC and AUC label-free quantitative methods in the analysis of autologous blood and semen exProteins from HIV- and HIV+ participants. Functional validation of the observations uncovered that semen exosomes (SE) but not blood exosomes (BE) are enriched in nucleic acid binding and cell adhesive factors. Our studies highlight that the protein composition of BE and SE are compositionally and functionally different. Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein?Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.