A targeted CRISPR screen identifies ETS1 as a regulator of HIV latency

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 3, 2024

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 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 primary CD4 T model. Interestingly, played divergent roles actively infected latently cells, knockout leading reduced but increased indicating can play both 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. Overall, these data demonstrate an important influences several cellular genes, including MALAT1, could have direct indirect

Язык: Английский

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Sustained antiviral response against in vitro HIV-1 infection in peripheral blood mononuclear cells from people with chronic myeloid leukemia treated with ponatinib

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Сен. 23, 2024

HIV-1 infection cannot be cured due to long-lived viral reservoirs formed by latently infected CD4 + T cells. “Shock and Kill” strategy has been considered eliminate the reservoir achieve a functional cure but stimulation of cytotoxic immunity is necessary. Ponatinib tyrosine kinase inhibitor (TKI) clinically used against chronic myeloid leukemia (CML) that demonstrated effective in vitro . Several TKIs may induce potent response cancer cells makes possible discontinue treatment people with CML who present long-term deep molecular response. In this longitudinal study, we analyzed capacity ponatinib an antiviral peripheral blood mononuclear (PBMCs) obtained from previously treated imatinib for median 10 years changed 12 months boost anticancer before discontinuing any TKI as part clinical trial NCT04043676. Participants were followed-up additional absence treatment. PBMCs at different time points then HIV-1. The rate was determined quantifying intracellular levels p24-gag p24-gag+ T−cells lower when these during after comparison those imatinib. Cytotoxicity HIV-infected target significantly higher than imatinib, it maintained least discontinuation. There significant negative correlation between cytotoxicity induced ponatinib. This mostly based on Natural Killer Tγδ seemingly boosted conclusion, transient immunomodulators like along ART could explored activity contribute elimination reservoir.

Язык: Английский

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Experimental Considerations for the Evaluation of Viral Biomolecular Condensates

Annual Review of Virology, Год журнала: 2024, Номер 11(1), С. 105 - 124

Опубликована: Сен. 26, 2024

Biomolecular condensates are nonmembrane-bound assemblies of biological polymers such as protein and nucleic acids. An increasingly accepted paradigm across the viral tree life is (a) that viruses form biomolecular (b) formation required for virus. Condensates can promote replication by promoting packaging, genome compaction, membrane bending, co-opting host translation. This review primarily concerned with exploring methodologies assessing virally encoded condensates. The goal this to provide an experimental framework virologists consider when designing experiments identify their components, reconstitute condensation cell free from minimal (c) ask questions about what conditions lead condensation, (d) map these back cycle, (e) design test inhibitors/modulators potential therapeutics. attempts integrate virology, biology, biochemistry approaches.

Язык: Английский

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