Advanced HIV-1 infection is commonly associated with progressive immune suppression and the development of cognitive, motor, and behavior disturbances. In its most severe form, it is diagnosed as HIV-1 associated dementia (HAD) and can progress to profound functional disability and death. Despite prodigious efforts to uncover biomarkers of HAD, none can adequately reflect disease onset or progression. Thus, we developed a proteomics platform for HAD biomarker discovery and used it to perform a pilot study on cerebrospinal fluid (CSF) from HIV-1-infected people with or without HAD. A 2-dimensional electrophoresis (2-DE) map of a HAD CSF proteome was focused on differentially expressed proteins. 2-DE difference gel electrophoresis (2-D DIGE) analysis showed >90 differences in protein spots of which 20 proteins were identified. Differential expression of 6 proteins was validated by Western blot tests and included vitamin D binding protein, clusterin, gelsolin, complement C3, procollagen C-endopeptidase enhancer 1, and cystatin C. We posit that these proteins, alone or together, are potential HAD biomarkers.

Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.