Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Correction for Lu et al., Screening for gene expression fluctuations reveals latency-promoting agents of HIV.

ABSTRACT:

SUBMITTER:

PROVIDER: S-EPMC9169741 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Correction for Lu et al., Screening for gene expression fluctuations reveals latency-promoting agents of HIV.

Proceedings of the National Academy of Sciences of the United States of America 20220408 15

PMID: 35394885

Similar Datasets

Screening for gene expression fluctuations reveals latency-promoting agents of HIV.

Project description:Upon treatment removal, spontaneous reactivation of latently infected T cells remains a major barrier toward curing HIV. Therapies that reactivate and clear the latent reservoir are only partially effective, while latency-promoting agents (LPAs) used to suppress reactivation and stabilize latency are understudied and lack diversity in their mechanisms of action. Here, we identify additional LPAs using a screen for gene-expression fluctuations (or "noise") that drive cell-fate specification and control HIV reactivation from latency. Single-cell protein dynamics of a minimal HIV gene circuit were monitored with time-lapse fluorescence microscopy. We screened 1,806 drugs, out of which 279 modulate noise magnitude or half autocorrelation time. Next, we tested the strongest noise modulators in a Jurkat T cell latency model and discovered three LPAs that would be overlooked by quantifying their mean expression levels alone. The LPAs reduced reactivation of latency in both Jurkat and primary cell models when challenged by synergistic and potent combinations of HIV activators. The two strongest LPAs, NSC 401005 and NSC 400938, are structurally and functionally related to inhibitors of thioredoxin reductase, a protein involved in maintaining redox balance in host cells. Experiments with multiple functional analogs revealed two additional LPAs, PX12 and tiopronin, and suggest a potential LPA family, within which some are commercially available and Food and Drug Administration-approved. The LPAs presented here may provide new strategies to complement antiretroviral treatments. Screening for gene expression noise holds the potential for drug discovery in other diseases.

| S-EPMC7980449 | biostudies-literature

Gene expression changes following latency reversal agents screening in a cellular model of HIV-1 latency

Project description:To delineate the mechanism driving JAK2 inhibitors´ induced effects on HIV-1 latency, whole transcriptome profiling was performed in the HIV-1 latency model HL-HIG, treated with the LRA fedratinib, the LPA pacritinib, the pan-JAKi ruxolitinib and PMA as a positive control of latency reactivation and immune activation.

2022-08-24 | GSE195855 | GEO

Mechanisms and efficacy of small molecule latency-promoting agents to inhibit HIV reactivation ex vivo.

Project description:Drugs that inhibit HIV transcription and/or reactivation of latent HIV have been proposed as a strategy to reduce HIV-associated immune activation or to achieve a functional cure, yet comparative studies are lacking. We evaluated 26 drugs, including drugs previously reported to inhibit HIV transcription (inhibitors of Tat-dependent HIV transcription, Rev, HSF-1/PTEF-b, HSP90, Jak/Stat, or SIRT1/Tat deacetylation) and other agents that were not tested before (inhibitors of PKC, NF-κB, SP-1, or histone acetyltransferase; NR2F1 agonists), elongation (inhibitors of CDK9/ PTEF-b), completion (inhibitors of PolyA-polymerase), or splicing (inhibitors of human splice factors). To investigate if those drugs would vary in their ability to affect different blocks to HIV transcription, we measured levels of initiated, elongated, midtranscribed, completed, and multiply spliced HIV RNA in PBMCs from antiretroviral therapy-suppressed individuals following ex vivo treatment with each drug and subsequent T cell activation. We identified new drugs that prevent HIV reactivation, including CDK and splicing inhibitors. While some drugs inhibited 1 or 2 steps, other drugs (CDK inhibitors, splicing inhibitors, tanespimycin, and triptolide) inhibited multiple stages of HIV transcription and blocked the production of supernatant viral RNA. These drugs and targets deserve further study in strategies aimed at reducing HIV-associated immune activation or achieving a functional cure.

| S-EPMC11466185 | biostudies-literature

Correction for Hraber et al., "Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments".

Project description: Not available

| S-EPMC5730795 | biostudies-literature

Reply to Soman et al, Alffenaar et al, Metcalfe et al, and Raoult.

Project description: Not available

| S-EPMC4696596 | biostudies-literature

Correction for Ferguson et al., General structural motifs of amyloid protofilaments

Project description: Not available

| S-EPMC1693757 | biostudies-literature

Correction for Graham et al., Phylogenetic structure in tropical hummingbird communities

Project description: Not available