Gene expression profiles at single cell level of CD4 T Cells infected with HIV Nano Cre
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE267462 | GEO | 2025/05/14
REPOSITORIES: GEO
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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.
2023-08-15 | GSE240894 | GEO
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.
2023-08-15 | GSE240896 | GEO
Project description:Despite effective treatment, HIV can persist in latent reservoirs, which represent a major obstacle towards HIV eradication. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of HIV infected cells. Here, we used a primary model of HIV latency and single-cell RNA sequencing to characterize transcriptional heterogeneity during HIV latency and reactivation. Our analysis identified transcriptional programs leading to successful reactivation of HIV expression. We further validated our results using primary CD4+ T cells isolated from HIV+ individuals.
2018-03-13 | GSE111727 | GEO
Project description:The epigenetic mechanisms established by histone modifications may affect the transcriptional silencing of HIV-1 and viral latency. A systematic epigenome profiling could be applicable to develop new epigenetic diagnostic markers for detecting HIV-1 latency. In this study, histone modification profiles of HIV-1 latency cell lines were compared with those of uninfected CD4+ T cell line. The HIV-1 latency gave rise to differential histone modification regions. The differential enrichment patterns helped us to define potential effector genes leading to the viral latency. The histone H3K4me3 and H3K9ac profiles were obtained from the HIV-1 latency cell lines (NCHA1, NCHA2, and ACH2) and control CD4+ T cell line (A3.01)
2014-06-06 | E-GEOD-58247 | biostudies-arrayexpress
Project description:Molecular mechanisms of HIV-1 latency have been studied extensively to achieve a functional cure for the acquired immunodeficiency syndrome (AIDS). To develop more promising latency-reversing agents (LRAs) to efficiently reactivate the latent reservoir which is subsequently eliminated by immune surveillance, new therapeutic targets need to be evaluated. Here, we found that the Polycomb group (PcG) protein CBX4 contributes to HIV-1 latency in many latency models and primary CD4+ T cells. CBX4 forms nuclear bodies with liquid–liquid phase separation (LLPS) properties on the HIV-1 long terminal repeat (LTR). Further proteomics analysis revealed that CBX4 recruits EZH2 to CBX4 bodies and SUMOylates EZH2 utilizing its SUMO E3 ligase activity, which enhances the H3K27 methyltransferase activity of EZH2. Our results indicated that CBX4 bridges the Polycomb repressive complex 1 (PRC1) and PRC2, resulting in synergistically maintaining HIV-1 latency. Dissolution of phase-separated CBX4 bodies could be a potential intervention to reactivate latent HIV-1.
2022-01-14 | PXD031011 |
Project description:Comparison of total RNA-seq data from ex vivo unstimulated and stimulated (with anti-CD3/CD28) cells from two primary cell models of HIV latency (resting-cell and wild-type virus models) and peripheral CD4+ T cells from HIV-infected ART-suppressed individuals (ex vivo cells). Two donors were analyzed per model.
2020-10-28 | GSE144585 | GEO
Project description:The barrier to HIV-1 functional cure is caused by a small pool of latently infected resting CD4 T-cells that persist under antiretroviral therapy. Notably this latent reservoir of infected cells will produce replication-competent infectious virus once prolonged suppressive HAART is withdrawn. The reactivation of HIV-1 gene expression in T-cells harboring latent provirus in HIV-1 patients under HAART will likely result in depletion of this latent reservoir due to cytopathic effects and immune clearance. Many studies have investigated small molecules that reactivate HIV-1 gene expression but to date no latency reversal agent (LRA) has been identified to be specific, non-toxic, and effective in primary T-cells isolated from HIV-1 infected individuals undergoing long-term HAART. Stochastic fluctuations in HIV-1 tat gene expression have been attributed to be essential in the viral progression to latency. We hypothesized that exposing Tat to latently infected CD4 T-cells will result in potent latency reversal. Our results indicate the capacity of an engineered Tat to reactivate HIV-1 in latently infected cells from patients to a similar degree as the protein kinase C agonist PMA (Phorbol 12-Myristate 13-Acetate) while showing no T-cell activation nor any significant transcriptome perturbation in primary CD4 T-cells.
2023-09-05 | GSE235229 | GEO
Project description:Although HIV-1 can directly infect resting CD4+ T cells, virus replication in resting CD4+T cells is very inefficient owing to the different host restriction factors blocking viral replication. The accessory protein Vpx from the major simian immunodeficiency virus (SIV) of rhesus macaque (mac) and HIV-2 lineage could degrade a host restriction factor, SAM and HD domain containing protein 1 (SAMHD1), to facilitate HIV reverse transcription. Interestingly, Vpx proteins from a second SIV lineage, the SIV of redcapped mangabeys or mandrills (SIVrcm/nmd-2), had no effect on SAMHD1 and did not affect the dNTP pool, but strongly increased HIV-1 infection in resting CD4+ T cells although not in primary macrophages. This indicates that Vpx, in addition to SAMHD1,can overcome a previously unexplored restriction factor for lentiviruses. Here to identify this potential restriction factor, we examined Vpxrcm-interacting cellular proteins and found that keratin 72 (KRT72), an intermediate filament protein that is exclusively expressed in resting CD4+ T cells, is a new host antiviral factor targeted by Vpx. Other than Vpx from SIV mac and HIV-2, the Vpxrcm/nmd-2 lineage, which had no effect on the SAMHD1 protein, could strongly promote the degradation of KRT72, resulting in enhanced HIV-1 infection in resting CD4+ T cells. Furthermore, we discovered that KRT72 restricts HIV-1 replication by sequestering incoming HIV-1 capsids in cytoplasmic intermediate filaments (IFs). In the presence of KRT72, HIV-1 capsid cores become attached to the IF and their trafficking toward the nucleus is inhibited. In contrast, in the absence of KRT72, HIV-1 capsids are transported into the nucleus,leading to high levels of integrated HIV-1 DNA. In addition, KRT72 expression was substantially higher in resting CD4+ T cells than in activated CD4+ T cells, and it was rapidly reduced by T cell activation. Collectively, the results show that KRT72 is a new Vpx-counteracted host antiviral factor that acts to tether incoming capsids to the cytoplasmic IF, thereby restricting HIV-1 infection in resting CD4+ T cells.
2025-03-28 | PXD059264 | Pride
Project description:Latent HIV reservoirs are extremely stable which pose a tremendous challenge to eradicate HIV. Here, we show that HIV explores the integrated stress response (ISR) signaling to establish its quiescent infection, refractory to the clearance for its persistence. HA15, a recently characterized specific ISR agonist, activates ATF4/CHOP signaling to not only disrupt HIV latency but also reduce HIV+ cells in the primary CD4+ T cell model of HIV latency without the induction of cell death in the HIV negative primary CD4+ T cells and the impact of viability in resting CD4+ T cells isolated from people living with HIV (PLWH). Mechanistically, the reduction of HIV+ cells by ISR/ATF4 activation is associated with the enhancement of cellular apoptosis. However, this mainly occurs in the HIV translation negative CD4+ T cells. In fact, ISR/ATF4 activation-induced cell death largely occurs in HIV transcription active (HIV gag-pol) CD4+ T cells. This is involved in HIV RNA-induced innate immune IFIT signaling. During the acute SIV infection in the rhesus macaques, the induction of ATF4 is associated with decrease of SIV reservoir in the intestine in vivo. When further tested in the resting CD4+ T cells isolated from PLWH on ART, the induction of ISR/ATF4 signaling by HA15 reduced HIV DNA reservoir. These findings support that inactivation of ISR/ATF4 signaling is associated with the maintenance of the stable and quiescent HIV reservoirs while enforced ISR/ATF4 signaling reduces translation quiescent HIV reservoirs in CD4+ T cells.
2022-12-05 | GSE210824 | GEO
Project description:Despite the success of antiretroviral therapy, HIV cannot be cured because of a reservoir of latently infected cells that evades therapy. To understand the mechanisms of HIV latency, we employed an integrated single-cell RNA-seq/ATAC-seq approach to simultaneously profile the transcriptomic and epigenomic characteristics of ~125,000 latently infected primary CD4 cells after reactivation using three different latency-reversing agents.
2023-12-28 | GSE242997 | GEO