(P25) Proteo-transcriptomics analysis of blood-cell populations with specific to HIV-infection

Författare/Medförfattare

Flora Mikaeloff, Anoop Ambikan, Anders Sönnerborg, Ujjwal Neogi,

Affiliates

Division of Clinical Microbiology, Department of Laboratory Medicine, ANA Futura Karolinska Institute, Stockholm, Sweden

Abstract

Background: Elite Controllers (EC) are a small subset of people living with HIV who can maintain suppressed viral loads for years without treatment. The EC status is considered to be dominated by the female, hypothetically due to hormones. Moreover, males seem more subject to loss of EC status. In an earlier study from the group, we observed a strong gender-specific difference in EC compared to healthy controls (HC) We hypothesize that males EC status is explained by complex rewiring in immune-related pathways.

Methods: To understand how EC males restrain HIV-replication compared to viral progressors (VP), transcriptome from peripheral blood mononuclear cell (PBMC) (9 EC and 9 VP) and proteome from PBMCs (9 EC and 9 VP) as well as isolated lymphocyte CD4+ and CD14+ T-cells (3EC and 3VP) populations were analyzed. Cell transcriptome profiling was used to determine the proportion of each immune cell type in PBMCs, to assure the homogeneity between samples and cluster immune cell types depending on gene expression. Differential genes expression analysis (DGE), Gene Ontology (GO) and feature selection using random forest were used to define better molecular mechanisms and biomarkers differing between EC and VP.

Results: Main cell types in PBMCs were T helper lymphocytes (LTCD4+) and monocytes (CD14+), which lead us to analyze isolated cell populations. Digital cell profiling highlighted that genes differentially expressed genes between EC and VP were associated with specific cell types concordant with HIV infection stages. Most pathways and genes identified were linked to immune system activation, cytokines production, apoptotic pathways, and cell surface receptors signaling. Pathways associated with metabolism and protein production were mostly involved in the difference between EC and VP in proteomics data.

Conclusions: This study allowed a better characterization of males EC at the cell population level. Loss of balance between these critical pathways could lead to a sex-dependent loss of elite controller status in males EC.