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

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dc.contributor.author Vansant, Gerlinde
dc.contributor.author Chen, Heng-Chang
dc.contributor.author Zorita, Eduard
dc.contributor.author Trejbalová, Katerina
dc.contributor.author Miklík, Dalibor
dc.contributor.author Filion, Guillaume
dc.contributor.author Debyser, Zeger
dc.date.accessioned 2020-10-16T06:34:03Z
dc.date.available 2020-10-16T06:34:03Z
dc.date.issued 2020
dc.identifier.citation Vansant G, Chen HC, Zorita E, Trejbalová K, Miklík D, Filion G, Debyser Z. The chromatin landscape at the HIV-1 provirus integration site determines viral expression. Nucleic Acids Res. 2020; 48(14):7801-17. DOI: 10.1093/nar/gkaa536
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/45497
dc.description.abstract HIV-1 persists lifelong in memory cells of the immune system as latent provirus that rebounds upon treatment interruption. Therefore, the latent reservoir is the main target for an HIV cure. Here, we studied the direct link between integration site and transcription using LEDGINs and Barcoded HIV-ensembles (B-HIVE). LEDGINs are antivirals that inhibit the interaction between HIV-1 integrase and the chromatin-tethering factor LEDGF/p75. They were used as a tool to retarget integration, while the effect on HIV expression was measured with B-HIVE. B-HIVE tracks insert-specific HIV expression by tagging a unique barcode in the HIV genome. We confirmed that LEDGINs retarget integration out of gene-dense and actively transcribed regions. The distance to H3K36me3, the marker recognized by LEDGF/p75, clearly increased. LEDGIN treatment reduced viral RNA expression and increased the proportion of silent provirus. Finally, silent proviruses obtained after LEDGIN treatment were located further away from epigenetic marks associated with active transcription. Interestingly, proximity to enhancers stimulated transcription irrespective of LEDGIN treatment, while the distance to H3K36me3 only changed after treatment with LEDGINs. The fact that proximity to these markers are associated with RNA expression support the direct link between provirus integration site and viral expression.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Nucleic Acids Res. 2020; 48(14):7801-17
dc.rights © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title The chromatin landscape at the HIV-1 provirus integration site determines viral expression
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkaa536
dc.subject.keyword Gene regulation
dc.subject.keyword Chromatin and epigenetics
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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