HIV infects mesenchymal stem cells (MSC) and modulates adipocyte differentiation

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

Congreso; IAS 2023, the 12th IAS Conference on HIV Science; 2023

Background: Mesenchymal stem cells (MSC) can differentiate into adipocytes and osteoblasts in a process that can be altered in pathological conditions,such as HIV infection. The objective was to determine if HIV could infect MSCs and modulate their differentiation into adipocytes or osteoblasts.Methods: To determine if these cells were susceptible to HIV infection, we evaluated the expression of the CD4 receptor and the CXCR4 and CCR5 coreceptors by flow cytometry in MSC. CCR5, through 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 study the expression of CCR5, CXCR4, and CD4at different times during the differentiation process.Cells were exposed to HIV (NL43 (X4) y AD8 (R5)) at an MOI of 0.5 pg (p24). The presence of the proviral genome in the MSCs was determined by Alu-PCR. Todetermine if HIV could modulate the differentiation of MSCs to adipocytes, cells were infected in the presence of differentiation medium (0.5mM3-Isobutyl-1-methylxanthine; 10ug/ml insulin; 0.01 dexamethasone uM) during 10 days. Lipid droplet formation was determined by confocal microscopy by staining withBodipy 493/503.Results: We show that MSC expresses CD4 and low levels of CXCR4 and CCR5. Assays of infectionindicated that both viral tropisms were capable of infecting MSC. After 7 days, we observedthat HIV modulated the differentiation of MSCs to adipocytes, observing differences betweenboth viral tropisms; HIV-AD8 was able to stimulate adipocyte differentiation, giving rise to larger lipid droplets, while HIV-NL43 induced the formation ofsmaller adipocytes with perinuclear lipid droplets. At 10 days of differentiation, both HIV tropisms gave rise to larger lipid droplets than uninfected controls.Our results indicated that CCR5 expression remained at the same levels throughout the differentiation process, while CXCR4 expression increased from day 7of differentiation, which could explain the differences observed between both viral tropisms.Conclusions: Together, our results indicate that HIV is capable to infect MSCs, preserving the presence of the proviral genome, and modulating thedifferentiation of these cells into adipocytes, presenting differences between the viral tropisms studied.