Galectin-1 promotes HIV-1 latency reactivation

JULIA RUBIONE; PEHUEN PEREYRA; GABRIEL DUETTE; ALAN ADAMCZYK; ALEJANDRO CAGNONI; NATALIA LAUFER; OMAR SUED; MATIAS OSTROWSKI; KARINA MARIÑO; PAULA PÉREZ; LUCÍA GUZMAN; YANINA GHIGLIONE; GABRIEL RABINOVICH

Mexico DF

Conferencia; 10th IAS Conference on HIV Science (IAS 2019); 2019

International AIDS Societty

Background: Galectin-1 (Gal-1) is an endogenous lectin with important immunomodulatory functions acting on both innate and adaptive immune cells. HIV-1 infects manly CD4+ T lymphocytes and macrophages causing CD4+T cell depletion, ultimately leading to acquired immunodeficiency syndrome (AIDS). Implementation of combination antiretroviral therapy (cART) significantly improves the prognosis of HIV-infected individuals. Nevertheless, chronic inflammation and the maintenance of latently infected cells-viral reservoir- represent two major barriers to achieve the cure of HIV infection. Herein, we analyzed the role of Galectin-1 on HIV-1 latency reactivation and chronic immune activation.Methods: Five clones of Jurkat T cells (J-LAT) were stimulated with recombinant Gal-1 and viral reactivation was assessed by analyzing GFP expression. The levels of Gal-1 in the plasma of HIV+ patients (N=62) classified in four groups (Baseline, chronic under treatment, chronic treatment naïve and elite controllers) was analyzed and compared with healthy donors (N=14). Cell-associated HIV DNA and unspliced (US)-RNA were quantified in purified CD4+ T cells by real-time PCR. Data were analyzed using nonparametric statistics.Results: Extracellular Gal-1 reverses HIV latency and activates viral replication in latently infected J-LAT cells by promoting Nf-kB activity and cell activation. In addition, in vitro treatment of CD4+T cells with Gal-1 increases the secretion of proinflammatory cytokines (IFNγ, TNFα and IL-6). Furthermore, we show that HIV-infected patients have increased plasma levels of Gal-1 as compared to healthy donors (p< 0.001). Longitudinal analysis of plasma samples confirmed the increased serum levels of Gal-1 during cART. Interestingly, we observed a positive correlation between Gal-1 levels and HIV reservoir size, as determined by US-RNA copy number (p< 0.01). Finally, we show that circulating extracellular vesicle induces the secretion of Gal-1 by macrophages, suggesting that this cell type could be responsible for the increase in plasma Gal-1.Conclusions: Gal-1 is capable of reversing HIV latency and this effect could be mediated by promotion of CD4+ T cell activation. Increased plasma levels of Gal-1 in patients and it´s correlation with reservoir size suggest that Gal-1 plays an important role in reservoir dynamics and in the pathogenesis of HIV-1 infection.