The chromatin landscape at the HIV-1 provirus integration site determines viral expression
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F20%3A00559755" target="_blank" >RIV/68378050:_____/20:00559755 - isvavai.cz</a>
Result on the web
<a href="https://academic.oup.com/nar/article/48/14/7801/5864711?login=true" target="_blank" >https://academic.oup.com/nar/article/48/14/7801/5864711?login=true</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/nar/gkaa536" target="_blank" >10.1093/nar/gkaa536</a>
Alternative languages
Result language
angličtina
Original language name
The chromatin landscape at the HIV-1 provirus integration site determines viral expression
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nucleic Acids Research
ISSN
0305-1048
e-ISSN
1362-4962
Volume of the periodical
48
Issue of the periodical within the volume
14
Country of publishing house
GB - UNITED KINGDOM
Number of pages
17
Pages from-to
7801-7817
UT code for WoS article
000574297400020
EID of the result in the Scopus database
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