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

• DOI: 10.1016/j.celrep.2014.12.047
• Publication Date: 2015-01-22T18:27:04Z
• Authors: Daniel Sauter; Dominik Hotter; Benoît Van Driessche; Christina M. Stürzel; Silvia F. Kluge; Steffen Wildum; Hangxing Yu; Bernd Baumann; Thomas Wirth; Jean-Christophe P...; Marie Leoz; Beatrice H. Hahn; Carine Van Lint; Frank Kirchhoff
• Keywords: Transcription; Viral life cycle; Viral protein

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