Apoptotic cell signaling in lymphocytes from HIV+ patients during successful therapy.
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.
Grelli
Sandro
S
Department of Experimental Medicine and Biochemical Science, University of Rome Tor Vergata, Via Montpellier 1, 00133 Roma, and Clinical Immunology Unit, S. Giovanni Hospital, Italy.
Balestrieri
Emanuela
E
Matteucci
Claudia
C
Minutolo
Antonella
A
D'Ettorre
Gabriella
G
Lauria
Filippo
F
Montella
Francesco
F
Vullo
Vincenzo
V
Vella
Stefano
S
Favalli
Cartesio
C
Mastino
Antonio
A
Macchi
Beatrice
B
D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D015398:Signal Transduction
D019380:Anti-HIV Agents