• Citer

Differential Regulation of NF-kB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins.

par Sauter, Daniel;Hotter, Dominik;Van Driessche, Benoît ;Stürzel, Christina M;Kluge, Silvia F;Wildum, Steffen;Yu, Hangxing;Baumann, Bernd;Wirth, Thomas;Plantier, Jean-Christophe;Leoz, Marie;Hahn, Beatrice H;Van Lint, Carine ;Kirchhoff, Frank
Référence Cell reports, 10, page (586-599)
Publication Publié, 2015

Article révisé par les pairs

• Accès en ligne
• Détails
• Contenu
• Statistiques

Résumé :

NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef. Although this effect of Vpu did not correlate with its ability to interact with β-TrCP, it involved the stabilization of IκB and reduced nuclear translocation of p65. Interestingly, however, Vpu did not affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was associated with increased NF-κB activation and induction of interferon and interferon-stimulated genes (ISGs) in HIV-1-infected T cells. Thus, HIV-1 and its simian precursors employ Nef to boost NF-κB activation early during the viral life cycle to initiate proviral transcription, while Vpu is used to downmodulate NF-κB-dependent expression of ISGs at later stages.