iTRAQ-based proteomic study discovered LAMP2 related to HIV-1 latency

To identify potential biomarkers related to HIV latency on the cell surface, a subcellular proteomic study was performed using an HIV-1 latency cell line (U1 (HIV-1-integrated U937 cell line)) and a control (U937). Differentially expressed proteins were analyzed using bioinformatics, followed by western blotting and multiple reaction monitoring of cell lines and/or resting CD4 + T cells from patients. The relationship between a differentially expressed protein (lysosome-associated membrane glycoprotein 2) and HIV-1 reactivation (by panobinostat) or a lysosomotropic agent (hydroxychloroquine) was studied. Totally, 110 differentially expressed proteins were identified in U1 cells compared with U937 cells. Bioinformatics analysis suggested that the immune response and phagosomes were associated with the altered proteins. LAMP2, leukocyte surface antigen CD47, CD55 and ITGA6 were downregulated in HIV-1 latent cells. LAMP2 was downregulated in enriched resting CD4 + T cells from patients infected with HIV. LAMP2 can be upregulated after HIV-1 reactivation and hydroxychloroquine stimulation. Our results indicated that the endosomal/lysosomal pathway was involved in HIV latency in macrophage cell lines. LAMP2 down-modulation was associated with HIV latency, and the re-expression of LAMP2 accompanied the viral latency/productive infection transition. This study offers new clues for understanding the mechanism of HIV-1 latency and the eradication of HIV reservoirs.