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Genomic profiling of HIV-1 integration in microglia cells links viral integration to the topologically associated domains

HIV-1 encounters the hierarchically organized host chromatin to stably integrate and persist in anatomically distinct latent reservoirs. The contribution of genome organization in HIV-1 infection has been largely understudied across different HIV-1 targets. Here, we determine HIV-1 integration sites...

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Main Authors: Rheinberger, Mona (Author) , Costa, Ana Luisa (Author) , Kampmann, Martin (Author) , Glavas, Dunja (Author) , Shytaj, Iart Luca (Author) , Sreeram, Sheetal (Author) , Penzo, Carlotta (Author) , Tibroni, Nadine (Author) , Garcia-Mesa, Yoelvis (Author) , Leskov, Konstantin (Author) , Fackler, Oliver Till (Author) , Vlahovicek, Kristian (Author) , Karn, Jonathan (Author) , Lucic, Bojana (Author) , Herrmann, Carl (Author) , Lusic, Marina (Author)
Format: Article (Journal)
Language:English
Published: 13 February 2023
In: Cell reports
Year: 2023, Volume: 42, Issue: 2, Pages: 1-27
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112110
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2023.112110
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723001213
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Author Notes:Mona Rheinberger, Ana Luisa Costa, Martin Kampmann, Dunja Glavas, Iart Luca Shytaj, Sheetal Sreeram, Carlotta Penzo, Nadine Tibroni, Yoelvis Garcia-Mesa, Konstantin Leskov, Oliver T. Fackler, Kristian Vlahovicek, Jonathan Karn, Bojana Lucic, Carl Herrmann, Marina Lusic
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Summary:HIV-1 encounters the hierarchically organized host chromatin to stably integrate and persist in anatomically distinct latent reservoirs. The contribution of genome organization in HIV-1 infection has been largely understudied across different HIV-1 targets. Here, we determine HIV-1 integration sites (ISs), associate them with chromatin and expression signatures at different genomic scales in a microglia cell model, and profile them together with the primary T cell reservoir. HIV-1 insertions into introns of actively transcribed genes with IS hotspots in genic and super-enhancers, characteristic of blood cells, are maintained in the microglia cell model. Genome organization analysis reveals dynamic CCCTC-binding factor (CTCF) clusters in cells with active and repressed HIV-1 transcription, whereas CTCF removal impairs viral integration. We identify CTCF-enriched topologically associated domain (TAD) boundaries with signatures of transcriptionally active chromatin as HIV-1 integration determinants in microglia and CD4+ T cells, highlighting the importance of host genome organization in HIV-1 infection.
Item Description:Gesehen am 21.03.2023
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112110

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