title: Blockade of BFA-mediated apoptosis in macrophages by the HIV-1 Nef protein.
abstract: 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.
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: W
authors.initials: W
authors.lastname: Abbas
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: K A
authors.initials: KA
authors.lastname: Khan
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: A
authors.identifier: 0000000273980498
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: M K
authors.initials: MK
authors.lastname: Tripathy
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: I
authors.initials: I
authors.lastname: Dichamp
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: M
authors.initials: M
authors.lastname: Keita
authors.affiliation: University of Heidelberg Medical Center, St. Lukas Klinik Solingen, Solingen D-42697, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Mahlknecht
authors.affiliation: Institut de Parasitologie et Pathologie Tropicale, EA 4438, Strasbourg University, 3 rue Koeberlé, Strasbourg 67000, France.
authors.forename: O
authors.initials: O
authors.lastname: Rohr
authors.affiliation: Department of Virology, Pathogens & Inflammation Laboratory, University of Franche-Comte, EA 4266, SFR FED 4234, CHRU Besancon, Besançon F-25030, France.
authors.forename: G
authors.initials: G
authors.lastname: Herbein
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020126:Brefeldin A / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D004351:Drug Resistance; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D012343:RNA, Transfer / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000097606:Exportin 1 Protein
chemical_list: D020126:Brefeldin A; D020169:Caspases; D045304:Cytochromes c; D028884:Karyopherins; D020648:Peptide Elongation Factor 1; D012343:RNA, Transfer; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C094814:EEF1A1 protein, human; C514837:nef protein, Human immunodeficiency virus 1