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Single-cell CRISPR Screen for HIV Host Dependency Factors Involved in Latency Reversal

ABSTRACT: Single-cell CRISPR Screen for HIV Host Dependency Factors Involved in Latency Reversal

PROVIDER: PRJNA1039800 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26815656_1.fastq.gz	Fastqsanger.gz
	SRR26815656_2.fastq.gz	Fastqsanger.gz
	SRR26815657_1.fastq.gz	Fastqsanger.gz
	SRR26815657_2.fastq.gz	Fastqsanger.gz
	SRR26815658_1.fastq.gz	Fastqsanger.gz

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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 [CRISPR]

Project description: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.

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