HIV MODULATES ADIPOCYTE DIFFERENTIATION VIA A MECHANISM DEPENDING ON VIRAL TROPISM

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

San Luis

Congreso; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología SAI; 2023

Sociedad Argentina de Inmunología

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 theirdifferentiation into adipocytes.To determine the susceptibility of MSC to HIV infection, we evaluated theexpression of the CD4 receptor and the CXCR4 and CCR5 co-receptors by flowcytometry. CCR5, along with its natural ligands CCL3, CCL4, and CCL5, inducesthe recruitment and differentiation of adipocytes. CXCL12 is the ligand of CXCR4and increases the sensitivity of adipocytes to insulin. Therefore, we decided toinvestigate the expression of CCR5, CXCR4, and CD4 at various time pointsduring the differentiation process (1,3, and 7 days). Infections were performedwith HIV-X4 (NL43) and –R5 (AD8) at a MOI of 0.5 pg (p24). To assess whetherHIV could modulate the differentiation of MSCs into adipocytes, cells wereinfected in the presence of differentiation medium (0.5mM 3-Isobutyl-1-methylxanthine; 10ug/ml insulin; 0.01 uM dexamethasone) for 10 days. Lipiddroplet formation was assessed by Bodipy 493/503 staining (Microscopy). Theexpression 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 ofCXCR4 (6.7 ± 0.43) and CCR5 (10.5 ± 0.56). After 7 days, we observed that HIVmodulated the differentiation of MSCs into adipocytes, with variations betweenthe two viral tropisms: HIV-R5 stimulated adipocyte differentiation, leading to thedevelopment of larger lipid droplets (p