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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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Hauptverfasser: Rheinberger, Mona (VerfasserIn) , Costa, Ana Luisa (VerfasserIn) , Kampmann, Martin (VerfasserIn) , Glavas, Dunja (VerfasserIn) , Shytaj, Iart Luca (VerfasserIn) , Sreeram, Sheetal (VerfasserIn) , Penzo, Carlotta (VerfasserIn) , Tibroni, Nadine (VerfasserIn) , Garcia-Mesa, Yoelvis (VerfasserIn) , Leskov, Konstantin (VerfasserIn) , Fackler, Oliver Till (VerfasserIn) , Vlahovicek, Kristian (VerfasserIn) , Karn, Jonathan (VerfasserIn) , Lucic, Bojana (VerfasserIn) , Herrmann, Carl (VerfasserIn) , Lusic, Marina (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 13 February 2023
In: Cell reports
Year: 2023, Jahrgang: 42, Heft: 2, Pages: 1-27
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112110
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2023.112110
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124723001213
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 21.03.2023
Beschreibung:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2023.112110

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