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Blockade of BFA-mediated apoptosis in macrophages by the HIV-1 Nef protein

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 relocalizat...

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Bibliographische Detailangaben
Hauptverfasser: Abbas, Wasim (VerfasserIn) , Khan, K. A. (VerfasserIn) , Kumar, A. (VerfasserIn) , Tripathy, M. K. (VerfasserIn) , Dichamp, I. (VerfasserIn) , Keita, M. (VerfasserIn) , Mahlknecht, Ulrich Rudolph (VerfasserIn) , Rohr, O. (VerfasserIn) , Herbein, G. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 February 2014
In: Cell death & disease
Year: 2014, Jahrgang: 5, Heft: 2
ISSN:2041-4889
DOI:10.1038/cddis.2014.16
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/cddis.2014.16
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/cddis201416
Volltext
Verfasserangaben:W. Abbas, K.A. Khan, A. Kumar, M.K. Tripathy, I. Dichamp, M. Keita, U. Mahlknecht, O. Rohr and G. Herbein
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 07.10.2020
Beschreibung:Online Resource
ISSN:2041-4889
DOI:10.1038/cddis.2014.16

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