A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency DOI Creative Commons
Manickam Ashokkumar, Terry L Hafer,

Abby Felton

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1012467 - e1012467

Published: April 8, 2025

Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between HIV-1 latency, we performed lentiviral CRISPR screen targeted set genes whose expression or activity correlates with expression. We further investigated one identified - factor ETS1, found it required for maintenance latency in both latently infected lines primary CD4 T model. Interestingly, ETS1 played divergent roles actively cells, knockout leading reduced but increased indicating can play positive negative role CRISPR/Cas9 cells from ART-suppressed people (PWH) confirmed maintains transcriptional repression clinical reservoir. Transcriptomic profiling ETS1-depleted PWH pathways involved are controlled resting cells. In particular, observed long non-coding RNA MALAT1 has been previously as regulator Furthermore, impact depletion on was partially dependent MALAT1. Additionally, demonstrate resulted enhanced abundance activating modifications (H3K9Ac, H3K27Ac, H3K4me3) histones located at terminal repeat (LTR), regulates chromatin-targeting complexes LTR. Overall, these data an important impacts through repressing regulating modification proviral histones.

Language: Английский

A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency DOI Creative Commons
Manickam Ashokkumar, Terry L Hafer,

Abby Felton

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(4), P. e1012467 - e1012467

Published: April 8, 2025

Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between HIV-1 latency, we performed lentiviral CRISPR screen targeted set genes whose expression or activity correlates with expression. We further investigated one identified - factor ETS1, found it required for maintenance latency in both latently infected lines primary CD4 T model. Interestingly, ETS1 played divergent roles actively cells, knockout leading reduced but increased indicating can play positive negative role CRISPR/Cas9 cells from ART-suppressed people (PWH) confirmed maintains transcriptional repression clinical reservoir. Transcriptomic profiling ETS1-depleted PWH pathways involved are controlled resting cells. In particular, observed long non-coding RNA MALAT1 has been previously as regulator Furthermore, impact depletion on was partially dependent MALAT1. Additionally, demonstrate resulted enhanced abundance activating modifications (H3K9Ac, H3K27Ac, H3K4me3) histones located at terminal repeat (LTR), regulates chromatin-targeting complexes LTR. Overall, these data an important impacts through repressing regulating modification proviral histones.

Language: Английский

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