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A CRISPR screen of HIV dependency factors reveals CCNT1 is non-essential in T cells but required for HIV-1 reactivation from latency.


ABSTRACT: We sought to explore the hypothesis that host factors required for HIV-1 replication also play a role in latency reversal. Using a CRISPR gene library of putative HIV dependency factors, we performed a screen to identify genes required for latency reactivation. We identified several HIV-1 dependency factors that play a key role in HIV-1 latency reactivation including ELL , UBE2M , TBL1XR1 , HDAC3 , AMBRA1 , and ALYREF . Knockout of Cyclin T1 ( CCNT1 ), a component of the P-TEFb complex important for transcription elongation, was the top hit in the screen and had the largest effect on HIV latency reversal with a wide variety of latency reversal agents. Moreover, CCNT1 knockout prevents latency reactivation in a primary CD4+ T cell model of HIV latency without affecting activation of these cells. RNA sequencing data showed that CCNT1 regulates HIV-1 proviral genes to a larger extent than any other host gene and had no significant effects on RNA transcripts in primary T cells after activation. We conclude that CCNT1 function is redundant in T cells but is absolutely required for HIV latency reversal.

SUBMITTER: Hafer TL 

PROVIDER: S-EPMC10402164 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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A CRISPR screen of HIV dependency factors reveals <i>CCNT1</i> is non-essential in T cells but required for HIV-1 reactivation from latency.

Hafer Terry L TL   Felton Abby A   Delgado Yennifer Y   Srinivasan Harini H   Emerman Michael M  

bioRxiv : the preprint server for biology 20230728


We sought to explore the hypothesis that host factors required for HIV-1 replication also play a role in latency reversal. Using a CRISPR gene library of putative HIV dependency factors, we performed a screen to identify genes required for latency reactivation. We identified several HIV-1 dependency factors that play a key role in HIV-1 latency reactivation including <i>ELL</i> , <i>UBE2M</i> , <i>TBL1XR1</i> , <i>HDAC3</i> , <i>AMBRA1</i> , and <i>ALYREF</i> . Knockout of Cyclin T1 ( <i>CCNT1</  ...[more]

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