Proteomic Profile Associated With Loss of Spontaneous Human Immunodeficiency Virus Type 1 Elite Control

与自发性人类免疫缺陷病毒 1 型精英控制丧失相关的蛋白质组学特征

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作者:Esther Rodríguez-Gallego, Laura Tarancón-Diez, Felipe García, Jorge Del Romero, Jose Miguel Benito, Verónica Alba, Pol Herrero, Anna Rull, Beatriz Dominguez-Molina, Onofre Martinez-Madrid, Luisa Martin-Pena, Federico Pulido, Agathe León, Carmen Rodríguez, Norma Rallón, Joaquim Peraire, Consuelo Vila

Background

Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The

Conclusions

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 ECs.

Methods

Plasma samples from ECs who spontaneously lost virological control (transient controllers [TCs]), at 2 years and 1 year before the loss of control, were compared with a control group of ECs who persistently maintained virological control during the same follow-up period (persistent controllers [PCs]). Comparative plasma shotgun proteomics was performed with tandem mass tag (TMT) isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry.

Results

Eighteen proteins exhibited differences comparing PC and preloss TC timepoints. 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, α-1-antichymotrypsin, ficolin-2, 14-3-3 protein, and galectin-3-binding protein were considered potential biomarkers. Conclusions: 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 ECs.

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