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

ABSTRACT: 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 (IS), associate them to 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, while CTCF removal impairs viral integration. We identify CTCF-enriched topologically associated domain (TAD) boundaries with signatures of transcriptionally active chromatin as HIV-1 integration determinant in microglia and CD4+ T cells, highlighting the importance of the host genome organization in HIV-1 infection.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223638 | GEO | 2023/01/24

REPOSITORIES: GEO

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