Integrative Proteo-Transcriptomic and Immunophenotyping Signatures of HIV-1 Elite Control Phenotype: A Cross-Talk Between Glycolysis and HIF Signaling

Abstract

Natural control of HIV-1 is a characteristic of <1% of HIV-1 infected individuals, so called Elite Controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found that HIF-signaling and glycolysis could be specific traits of the EC phenotype with upregulation of ENO1. Also, dysregulation of HIF target genes was identified as a specific feature of the EC group. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4+ and CD8+ T cells in the male EC was observed, indicating increased activation of the HIF-signaling pathway while females exhibited increased activation of Akt phosphorylation. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile in EC.