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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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Detalles Bibliográficos
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
Descripción
Sumario: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.