Proteomic Profile Associated with Loss of Spontaneous HIV-1 Elite Control.

Background: Elite Controllers (EC) spontaneously control plasma HIV-1-RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers.

Methods: Plasma samples from EC who spontaneously lost virological control (Transient Controllers, TC), at two and one year before the loss of control, were compared with a control group of EC who persistently maintained virological control during the same follow-up period (Persistent Controllers, PC). Comparative plasma shotgun proteomics was performed with TMT isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry.

Results: Eighteen proteins exhibited differences comparing PC and pre-loss TC time points. These proteins were involved in proinflammatory mechanisms and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, Alpha-1-antichymotrypsin, Ficolin-2, 14-3-3 protein and Galectin-3-binding protein were considered potential biomarkers.

Conclusion: The proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration and coagulation. Galectin-3-binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in EC.