CRISPR-based gene knockout screens reveal deubiquitinases involved in HIV-1 latency in two Jurkat cell models.
In: Scientific Reports, Jg. 10 (2020-03-24), Heft 1, S. 1-14
Online
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Zugriff:
The major barrier to a HIV-1 cure is the persistence of latent genomes despite treatment with antiretrovirals. To investigate host factors which promote HIV-1 latency, we conducted a genome-wide functional knockout screen using CRISPR-Cas9 in a HIV-1 latency cell line model. This screen identified IWS1, POLE3, POLR1B, PSMD1, and TGM2 as potential regulators of HIV-1 latency, of which PSMD1 and TMG2 could be confirmed pharmacologically. Further investigation of PSMD1 revealed that an interacting enzyme, the deubiquitinase UCH37, was also involved in HIV-1 latency. We therefore conducted a comprehensive evaluation of the deubiquitinase family by gene knockout, identifying several deubiquitinases, UCH37, USP14, OTULIN, and USP5 as possible HIV-1 latency regulators. A specific inhibitor of USP14, IU1, reversed HIV-1 latency and displayed synergistic effects with other latency reversal agents. IU1 caused degradation of TDP-43, a negative regulator of HIV-1 transcription. Collectively, this study is the first comprehensive evaluation of deubiquitinases in HIV-1 latency and establishes that they may hold a critical role. [ABSTRACT FROM AUTHOR]
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CRISPR-based gene knockout screens reveal deubiquitinases involved in HIV-1 latency in two Jurkat cell models.
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Autor/in / Beteiligte Person: | Rathore, Anurag ; Iketani, Sho ; Wang, Pengfei ; Jia, Manxue ; Sahi, Vincent ; Ho, David D. |
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Zeitschrift: | Scientific Reports, Jg. 10 (2020-03-24), Heft 1, S. 1-14 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 2045-2322 (print) |
DOI: | 10.1038/s41598-020-62375-3 |
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