Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA168298 | ENA |
REPOSITORIES: ENA
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Project description:miRNA profiling in HIV-1 latently infected cells
| PRJNA167946 | ENA
Project description:Gene expression profiling of HIV-1 latently infected memory CD4+ T cells
| PRJNA175322 | ENA
Project description:Background: The cellular reservoir of latent HIV infection remains the main barrier to cure this virus. Elimination of this reservoir would be possible, if molecular identity of latently infected cells were fully elucidated. Biomarkers proposed previously were able to capture only a relatively small fraction of all reservoir cells. In the present study, we set out to conduct comprehensive molecular profiling, at the protein and RNA levels, of CD4+ T cells latently infected with HIV in vitro, using liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing (RNA-Seq), respectively. Protein-based methods such as quantitative proteomic profiling using LC-MS may be more beneficial due to direct transferability of results to antibody-based approaches to capture latently infected cells. Integrated analysis of proteomic and transcriptomic data adds a level of validation and increases confidence in identified biomarkers. Flow cytometry and integrated HIV DNA assay were further used to enrich for latently infected cells with antibodies against selected biomarker proteins. Results: Using quantitative proteomics, we identified a total of 10,886 proteins (peptide level FDR < 0.05), of which 673 were up- and 780 down-regulated in latently infected compared to mock-infected cells in vitro (p < 0.05). Among these proteins, 21 were dysregulated at the RNA level in the same direction. Pathway analysis identified p53, mTOR, Wnt and NOTCH signaling, demonstrating that our in vitro model reflects known mechanisms of latency establishment and maintenance. Comparison of identified proteins with other proteomics studies revealed that identified molecular signatures of latency depend on technology and cell types used; however, a subset of proteins were identified both in the present, and at least one other study. Antibodies against selected protein markers, CEACAM1 and PLXNB2, could enrich for latently infected cells from mixed cell population 3-10 fold (5.8 fold average, p < 0.001). Conclusion: Two new molecules, CEACAM1 and PLXNB2, were identified as biomarkers for HIV latency. However, the level of enrichment for latently infected cells compared to biomarkers proposed previously was not improved. These results are consistent with the idea that each proposed biomarker defines only a subset of latently infected cells, and that a combined biomarker will be required to capture or target the latent HIV reservoir represented by different cell types.
2023-10-24 | PXD024014 | Pride
Project description:Genome-wide analysis of histone modifications in latently HIV-1 infected T cells
| PRJNA251729 | ENA
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
Project description:HIV infection is not curable due to viral latency. Compelling reports studying proteins such as CD2, PD-1, LAG-3 and TIGIT suggest that there is a distinct profile of surface proteins that can be used for targeting latently infected cells. We have recently reported that glycoproteins were differentially secreted from HIV latently infected ACH-2 cells compared to the parental A3.01 cells. This observation suggests that glyco-phenotype might be different in these two cell lines. To determine the difference, the ACH-2 and A3.01 cell lines were subjected to a glycoproteomic analysis. A total number of 940 unique N-linked glycosite-containing peptides from 515 glycoproteins were identified. Among the glycoproteins, 365 and 104 were annotated as cell surface and membrane-associated proteins, respectively. Label free quantitative LC-MS/MS analysis revealed a change of 236 glycosite-containing peptides from 172 glycoproteins between the two cell lines without reactivation. Bioinformatic analysis suggests that cell adhesion, immune response, glycoprotein metabolic process, cell motion and cell activation were associated with the changed proteins. After reactivation of latency by phorbol myristate acetate (PMA), changes in glycosite-containing peptides were observed in both cell lines. Changes in 49 glycosite-containing peptides from 45 glycoproteins might be due to viral replication. The changed proteins suggest that cell migration, response to wounding and immune response were impaired in reactivated latently infected cells. Our study provides important glycoproteomic data in respect to HIV latently infected cells. Glycoproteomics merits future application using primary cells to discover reveal mechanisms in HIV pathogenesis.
2016-05-23 | PXD003561 | Pride
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | 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