Blockade of BFA-mediated apoptosis in macrophages by the HIV-1 Nef protein.
Fiche publication
Date publication
février 2014
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBEIN Georges, Pr ROHR Olivier
Tous les auteurs :
Abbas W, Khan KA, Kumar A, Tripathy MK, Dichamp I, Keita M, Mahlknecht U, Rohr O, Herbein G
Lien Pubmed
Résumé
HIV-1 Nef protein has key roles at almost all stages of the viral life cycle. We assessed the role of Nef and of the translation elongation factor eEF1A in primary human macrophages. Nuclear retention experiments and inhibition of the exportin-t (Exp-t) pathway suggested that cytoplasmic relocalization of eEF1A, mediated by Exp-t occurs in Nef-treated monocyte-derived macrophages (MDMs). We observed the presence of tRNA in the Nef/eEF1A complexes. Nucleocytoplasmic relocalization of the Nef/eEF1A complexes prevented stress-induced apoptosis of MDMs treated with brefeldin A. Blockade of stress-induced apoptosis of MDMs treated with HIV-1 Nef resulted from enhanced nucleocytoplasmic transport of eEF1A with decreased release of mitochondrial cytochrome c, and from increased tRNA binding to cytochrome c, ultimately leading to an inhibition of caspase activation. Our results indicate that HIV-1 Nef, through the nucleocytoplasmic relocalization of eEF1A and tRNAs, enhances resistance to stress-induced apoptosis in primary human macrophages.
Mots clés
Apoptosis, drug effects, Brefeldin A, pharmacology, Caspases, metabolism, Cells, Cultured, Cytochromes c, metabolism, Drug Resistance, Humans, Karyopherins, genetics, Macrophages, drug effects, Mitochondria, metabolism, Peptide Elongation Factor 1, genetics, Protein Interaction Domains and Motifs, Protein Transport, RNA Interference, RNA, Transfer, metabolism, Receptors, Cytoplasmic and Nuclear, genetics, Recombinant Proteins, metabolism, Time Factors, Transfection, nef Gene Products, Human Immunodeficiency Virus, genetics
Référence
Cell Death Dis. 2014 Feb;5:e1080