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

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 activat...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682570/
https://www.ncbi.nlm.nih.gov/pubmed/25620704
http://dx.doi.org/10.1016/j.celrep.2014.12.047
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author 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
author_facet 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
author_sort Sauter, Daniel
collection PubMed
description 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.
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spelling pubmed-46825702015-12-17 Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins 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 Cell Rep Article 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. 2015-01-22 2015-02-03 /pmc/articles/PMC4682570/ /pubmed/25620704 http://dx.doi.org/10.1016/j.celrep.2014.12.047 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
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
Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title_full Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title_fullStr Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title_full_unstemmed Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title_short Differential Regulation of NF-κB-Mediated Proviral and Antiviral Host Gene Expression by Primate Lentiviral Nef and Vpu Proteins
title_sort differential regulation of nf-κb-mediated proviral and antiviral host gene expression by primate lentiviral nef and vpu proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682570/
https://www.ncbi.nlm.nih.gov/pubmed/25620704
http://dx.doi.org/10.1016/j.celrep.2014.12.047
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