title: Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins.
abstract: 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.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Electronic address: daniel.sauter@uni-ulm.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauter
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hotter
authors.affiliation: Institute for Molecular Biology and Medicine, University of Brussels, 6041 Gosselies, Belgium.
authors.forename: Benoît
authors.initials: B
authors.lastname: Van Driessche
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Kluge
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Wildum
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Hangxing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Physiological Chemistry, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Baumann
authors.affiliation: Institute of Physiological Chemistry, Ulm University Medical Center, 89081 Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.affiliation: Laboratoire Associé au Centre National de Référence du VIH, 76031 Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Plantier
authors.affiliation: Laboratoire Associé au Centre National de Référence du VIH, 76031 Rouen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Leoz
authors.affiliation: Departments of Medicine and Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: Institute for Molecular Biology and Medicine, University of Brussels, 6041 Gosselies, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany. Electronic address: frank.kirchhoff@uni-ulm.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000818:Animals; D015870:Gene Expression; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology; D017958:Lentiviruses, Primate / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D014764:Viral Proteins; D051550:I-kappa B Kinase