Apoptotic cell signaling in lymphocytes from HIV+ patients during successful therapy

Abstract

The impact of antiretroviral therapy (ART) on immune-reconstitution and its relationship with the complex scenario of multiple cell signaling associated with apoptosis in HIV infection has not yet been fully elucidated. Here we report the results of the analysis of the expression of 13 genes involved in the apoptotic pathway, simultaneously detected by RNA-protection assay in peripheral blood mononuclear cells (PBMCs) of 12 HIV-1-infected responder patients before and during successful ART. In particular, we calculated the correlations among apoptosis and viral load (VL) levels versus the quantitative expression of genes associated with death receptors or to Bcl-2 pathways. Nonparametric bivariate Spearman's analysis of significant correlations showed that apoptosis was directly correlated with mRNA levels for caspase-8, FasL, and TRAIL. Conversely, apoptosis levels were inversely correlated with mRNA levels for Bcl-xl, Bcl-2, and Mcl-1, respectively. In addition, while VL was directly correlated with the expression of caspase 8, it was inversely correlated with mRNA levels for Bcl-2 and Mcl-1. These results, although worthy of further investigation, show that variations of apoptosis levels in PBMCs of HIV-1 + patients during ART are strictly related to the modulation of a complex network of signaling involving both death and survival of lymphocytes. © 2006 New York Academy of Sciences.