The chromatin landscape at the HIV-1 provirus integration site determines viral expression

We investigated the link between HIV-1 integration by using B-HIVE and LEDGINs. B-HIVE tracks insert-specific HIV expression by tagging a unique barcode in the HIV genome. LEDGINs are antivirals that inhibit the interaction between HIV-IN and its chromatin tethering cofactor LEDGF/p75. They are known to retarget HIV-1 integration sites. Here, we confirmed that LEDGIN treatment retargets integration out of transcriptionally active regions and reduce HIV expression. Silent provirus was located at increased distance to H3K36me3, the recognition marker of LEDGF/p75, after treatment with LEDGINs. Viral RNA expression was also influenced by the proximity of enhancers, regardless of the presence of LEDGINs. Genomic DNA and RNA was extracted from SupT1 and Jurkat cells 14 days after transduction with barcoded HIV in the presence of varying concentrations of LEDGIN CX014442 (6.25, 15.62 or 31.25µM).