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

Autor: Daniel Sauter, Dominik Hotter, Benoît Van Driessche, Christina M. Stürzel, Silvia F. Kluge, Steffen Wildum, Hangxing Yu, Bernd Baumann, Thomas Wirth, Jean-Christophe Plantier, Marie Leoz, Beatrice H. Hahn, Carine Van Lint, Frank Kirchhoff
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Cell Reports, Vol 10, Iss 4, Pp 586-599 (2015)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2014.12.047
Popis: 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.
Databáze: Directory of Open Access Journals