HIV MODULATES ADIPOCYTE DIFFERENTIATION VIA A MECHANISM DEPENDING ON VIRAL TROPISM

NICOLE FREIBERGER; ALICIA LOPEZ; FRANCO SVIERCZ; ALEX GUANO; CINTIA CEVALLOS; PATRICIO JARMOLUK; BELÉN PALMA; MARCELA GARCÍA; JORGE QUARLERI; M. VICTORIA DELPINO

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) 9 -11 de noviembre de 2023 Universidad Nacional de San Luis-San Luis; 2023

Mesenchymal stem cells (MSC) can differentiate into adipocytes and osteoblasts, a process that can be altered in pathological conditions, such as HIV infection. The aim was to determine whether HIV can infect MSCs and modulate their differentiation into adipocytes.To determine the susceptibility of MSC to HIV infection, we evaluated the expression of the CD4 receptor and the CXCR4 and CCR5 co-receptors by flow cytometry. CCR5, along with its natural ligands CCL3, CCL4, and CCL5, induces the recruitment and differentiation of adipocytes. CXCL12 is the ligand of CXCR4 and increases the sensitivity of adipocytes to insulin. Therefore, we decided to investigate the expression of CCR5, CXCR4, and CD4 at various time points during the differentiation process (1,3, and 7 days). Infections were performed with HIV-X4 (NL43) and –R5 (AD8) at a MOI of 0.5 pg (p24). To assess whether HIV could modulate the differentiation of MSCs into adipocytes, cells were infected in the presence of differentiation medium (0.5mM 3-Isobutyl-1-methylxanthine; 10ug/ml insulin; 0.01 uM dexamethasone) for 10 days. Lipid droplet formation was assessed by Bodipy 493/503 staining (Microscopy). The expression of master transcription factors implicated in adipogenesis (PPARγ, C/EBPβ, and C/EBPα) were evaluated using RT-qPCR. We demonstrated that MSCs express CD4 (7.63 ± 0.94) and exhibit low levels of CXCR4 (6.7 ± 0.43) and CCR5 (10.5 ± 0.56). After 7 days, we observed that HIV modulated the differentiation of MSCs into adipocytes, with variations between the two viral tropisms: HIV-R5 stimulated adipocyte differentiation, leading to the development of larger lipid droplets (p