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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 2, Pp 112110- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112110
Popis: 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.
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