HIV-1-induced manipulation of CD4+ T cell glycolytic activity promotes L-lactic acid-mediated depletion of CD4+T cells

DUETTE, GABRIEL; PALMER, CLOVIS; PEREYRA GERBER, PEHUEN; RUBIONE, JULIA; ERRA DIAZ, FERNANDO; DANTAS, EZEQUIEL; VARESE, AUGUSTO; MATIAS OSTROWSKI

Buenos Aires

Congreso; Reunion Anual de la Sociedad Argentina de Inmunologia. Reunion de la sociedad Franco-Argentina de Inmunologia; 2015

Sociedad Argentina de Inmunologia

Background: In the absence of antiretroviral drugs, persistent HIV-1 infection causes dysfunction and progressive loss of CD4+ T cells, leading to the development of AIDS. The pathogenic mechanism responsible for CD4+ T cell functional dysregulation and death are still unclear. Herein, we investigated the modulation of glucose metabolism by HIV-1 infection and its relationship with CD4+ T cell depletion.Methods: CD4+ T cells from healthy donors were isolated from blood, activated in vitro and subsequently infected with HIV-1. At day 5 post-infection, cell viability was analyzed by Annexin V/7-AAD staining. Glucose metabolism was analyzed by quantifying glucose uptake and L-Lactic acid production. Hypoxia-inducible factor 1a (HIF-1ï¡) and mTOR activities were analyzed by different cellular and biochemical approaches. Results: HIV-1 infection induces an increase (p