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An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins

Subtype C is the most prevalent clade of human immunodeficiency virus type 1 (HIV-1) worldwide. The reasons for this are poorly understood. Here, we demonstrate that a characteristic additional third nuclear factor κB (NF-κB) binding site in the long terminal repeat (LTR) promoter allows subtype C H...

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Autores principales: Bosso, Matteo, Stürzel, Christina M., Kmiec, Dorota, Badarinarayan, Smitha Srinivasachar, Braun, Elisabeth, Ito, Jumpei, Sato, Kei, Hahn, Beatrice H., Sparrer, Konstantin M.J., Sauter, Daniel, Kirchhoff, Frank
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505707/
https://www.ncbi.nlm.nih.gov/pubmed/34551301
http://dx.doi.org/10.1016/j.celrep.2021.109735
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author Bosso, Matteo
Stürzel, Christina M.
Kmiec, Dorota
Badarinarayan, Smitha Srinivasachar
Braun, Elisabeth
Ito, Jumpei
Sato, Kei
Hahn, Beatrice H.
Sparrer, Konstantin M.J.
Sauter, Daniel
Kirchhoff, Frank
author_facet Bosso, Matteo
Stürzel, Christina M.
Kmiec, Dorota
Badarinarayan, Smitha Srinivasachar
Braun, Elisabeth
Ito, Jumpei
Sato, Kei
Hahn, Beatrice H.
Sparrer, Konstantin M.J.
Sauter, Daniel
Kirchhoff, Frank
author_sort Bosso, Matteo
collection PubMed
description Subtype C is the most prevalent clade of human immunodeficiency virus type 1 (HIV-1) worldwide. The reasons for this are poorly understood. Here, we demonstrate that a characteristic additional third nuclear factor κB (NF-κB) binding site in the long terminal repeat (LTR) promoter allows subtype C HIV-1 strains to evade restriction by nuclear PYHIN proteins, which sequester the transcription factor Sp1. Further, other LTR alterations are responsible for rare PYHIN resistance of subtype B viruses. Resistance-conferring mutations generally reduce the dependency of HIV-1 on Sp1 for virus production and render LTR transcription highly responsive to stimulation by NF-κB/p65. A third NF-κB binding site increases infectious virus yield in primary CD4(+) T cells in an γ-interferon-inducible protein 16 (IFI16)-dependent manner. Comprehensive sequence analyses suggest that the frequency of circulating PYHIN-resistant HIV-1 strains is increasing. Our finding that an additional NF-κB binding site in the LTR confers resistance to nuclear PYHIN proteins helps to explain the dominance of clade C HIV-1 strains.
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spelling pubmed-85057072021-10-12 An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins Bosso, Matteo Stürzel, Christina M. Kmiec, Dorota Badarinarayan, Smitha Srinivasachar Braun, Elisabeth Ito, Jumpei Sato, Kei Hahn, Beatrice H. Sparrer, Konstantin M.J. Sauter, Daniel Kirchhoff, Frank Cell Rep Article Subtype C is the most prevalent clade of human immunodeficiency virus type 1 (HIV-1) worldwide. The reasons for this are poorly understood. Here, we demonstrate that a characteristic additional third nuclear factor κB (NF-κB) binding site in the long terminal repeat (LTR) promoter allows subtype C HIV-1 strains to evade restriction by nuclear PYHIN proteins, which sequester the transcription factor Sp1. Further, other LTR alterations are responsible for rare PYHIN resistance of subtype B viruses. Resistance-conferring mutations generally reduce the dependency of HIV-1 on Sp1 for virus production and render LTR transcription highly responsive to stimulation by NF-κB/p65. A third NF-κB binding site increases infectious virus yield in primary CD4(+) T cells in an γ-interferon-inducible protein 16 (IFI16)-dependent manner. Comprehensive sequence analyses suggest that the frequency of circulating PYHIN-resistant HIV-1 strains is increasing. Our finding that an additional NF-κB binding site in the LTR confers resistance to nuclear PYHIN proteins helps to explain the dominance of clade C HIV-1 strains. 2021-09-21 /pmc/articles/PMC8505707/ /pubmed/34551301 http://dx.doi.org/10.1016/j.celrep.2021.109735 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Bosso, Matteo
Stürzel, Christina M.
Kmiec, Dorota
Badarinarayan, Smitha Srinivasachar
Braun, Elisabeth
Ito, Jumpei
Sato, Kei
Hahn, Beatrice H.
Sparrer, Konstantin M.J.
Sauter, Daniel
Kirchhoff, Frank
An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title_full An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title_fullStr An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title_full_unstemmed An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title_short An additional NF-κB site allows HIV-1 subtype C to evade restriction by nuclear PYHIN proteins
title_sort additional nf-κb site allows hiv-1 subtype c to evade restriction by nuclear pyhin proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505707/
https://www.ncbi.nlm.nih.gov/pubmed/34551301
http://dx.doi.org/10.1016/j.celrep.2021.109735
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