Alpha-1 antitrypsin variants in plasma from HIV-infected patients revealed by proteomic and glycoproteomic analysis.

ABSTRACT

Novel tools are necessary to explore proteins related to human immunodeficiency virus (HIV) infection. In this work, proteomic and glycoproteomic technology were employed to examine plasma samples from HIV-positive patients. Through comparative proteome analysis of normal and HIV-positive plasma samples, 19 differentially expressed protein spots related to 12 non-redundant proteins were identified by ESI-ion trap MS. Among these, the 130-kDa isoform of α-1-antitrypsin was found to be decreased in HIV-positive patients while another variant with a molecular weight of 40 kDa was increased. SWISS-2-D-PAGE reference gel and protein sequence comparisons of the 40-kDa protein showed homology with α-1-antitrypsin minus the N-terminus, and its identity was further confirmed by 1-D Western blotting and glycoproteomic analysis. In all, our results showed that proteomics and glycoproteomics are powerful tools for discovering proteins related to HIV infection. Furthermore, this 40-kDa variant of α-1-antitrypsin found in the plasma of HIV-positive individuals may prove to be a potentially useful biomarker for anti-HIV research according to bioinformatics analysis.