Genome-wide analysis of histone modifications in latently HIV-1 infected T cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58247 | GEO | 2014/06/06
SECONDARY ACCESSION(S): PRJNA251729
REPOSITORIES: GEO
Similar Datasets
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:Herein expression trends of host miRNA were measured in HIV-1 latently infected and persistent replication cells, as well as the control cells. HIV-1 latency infection was established by infecting CEM-SS lymphocytes with HIV-1 Bru strain. After selection and long-term culture, the chronically infected cell showed the characteristics of latency definition: 1. The provirus was intergrated in to the host genome.2. No viral expression could be detected during culture.3 .Cell stimulators, such as TNFa,PMA, etc, reactivate the viral expression. As expected, miRNA trend was different in HIV-1 latency when compared to the control or HIV-1 replication. A subset of miRNAs is enriched in HIV-1 latency model. The observation reinforces the concept of active HIV-1 interplay with host small RNAs that modulate HIV-1 infection mode. In this study, the in vitro steady cell culture was used to explore the miRNA transcription signatures in HIV-1 infection. miRNA profiles were performed and compared among normal control,HIV-1 latency and HIV-1 replication .
2012-12-01 | E-GEOD-38388 | biostudies-arrayexpress
Project description:Herein expression trends of host miRNA were measured in HIV-1 latently infected and persistent replication cells, as well as the control cells. HIV-1 latency infection was established by infecting CEM-SS lymphocytes with HIV-1 Bru strain. After selection and long-term culture, the chronically infected cell showed the characteristics of latency definition: 1. The provirus was intergrated in to the host genome.2. No viral expression could be detected during culture.3 .Cell stimulators, such as TNFa,PMA, etc, reactivate the viral expression. As expected, miRNA trend was different in HIV-1 latency when compared to the control or HIV-1 replication. A subset of miRNAs is enriched in HIV-1 latency model. The observation reinforces the concept of active HIV-1 interplay with host small RNAs that modulate HIV-1 infection mode.
2012-12-01 | GSE38388 | GEO
Project description:Suppressive HAART does not eradicate HIV-1 and viral DNA persists as a stably integrated form in the absence of viral particle production. As a consequence, latent reservoirs are refractory to antiretroviral drugs and invisible to immune surveillance. The largest latent reservoir consists of resting memory CD4+ T cells. These cells can resume viral infection when activated through antigen recognition, causing bursts of viremia (blips). Current therapies targeting latent HIV-1 have focused primarily on the “shock and kill” approach, which employs “anti-latency” drugs – most notably histone deacetylase (HDAC) inhibitors – to reactivate and flush latent provirus from its cellular reservoirs in the absence of global T cell activation. This approach is predicated on the notions that viral reactivation will lead to the demise of the infected cell, and that HAART will prevent spreading of the infection. On the contrary, recent evidence indicates that latently infected CD4+ T cells of HIV-1 patients on HAART survive in vitro viral reactivation with the HDAC inhibitor, SAHA, even when co-cultured with autologous CD8+ cytotoxic T lymphocytes (CTL). Moreover, it remains to be addressed the impact of anti-latency drugs on viral reservoirs undergoing low-level ongoing replication, inherently more resistant to the cytopathic effects of HIV-1 and residing in anatomical sites hard to reach for some antiretroviral drugs (e.g. macrophages). As a consequence, there is a need to develop alternative therapeutic approaches aimed at eliminating or decreasing the latent reservoir. Progress in that direction has been hindered by the lack of biomarkers uniquely or differentially expressed on latently infected compared to their uninfected counterparts. To gain insight into the cellular mechanisms that take place in the context of latency, and with the goal of identifying distinctive markers that distinguish latently infected CD4+ T cells, we have used an in vitro model developed in our laboratory to study the expression profile of latently infected CD4+ T cells by microarray analysis.
2013-03-15 | GSE40550 | GEO
Project description:Suppressive HAART does not eradicate HIV-1 and viral DNA persists as a stably integrated form in the absence of viral particle production. As a consequence, latent reservoirs are refractory to antiretroviral drugs and invisible to immune surveillance. The largest latent reservoir consists of resting memory CD4+ T cells. These cells can resume viral infection when activated through antigen recognition, causing bursts of viremia (blips). Current therapies targeting latent HIV-1 have focused primarily on the M-bM-^@M-^\shock and killM-bM-^@M-^] approach, which employs M-bM-^@M-^\anti-latencyM-bM-^@M-^] drugs M-bM-^@M-^S most notably histone deacetylase (HDAC) inhibitors M-bM-^@M-^S to reactivate and flush latent provirus from its cellular reservoirs in the absence of global T cell activation. This approach is predicated on the notions that viral reactivation will lead to the demise of the infected cell, and that HAART will prevent spreading of the infection. On the contrary, recent evidence indicates that latently infected CD4+ T cells of HIV-1 patients on HAART survive in vitro viral reactivation with the HDAC inhibitor, SAHA, even when co-cultured with autologous CD8+ cytotoxic T lymphocytes (CTL). Moreover, it remains to be addressed the impact of anti-latency drugs on viral reservoirs undergoing low-level ongoing replication, inherently more resistant to the cytopathic effects of HIV-1 and residing in anatomical sites hard to reach for some antiretroviral drugs (e.g. macrophages). As a consequence, there is a need to develop alternative therapeutic approaches aimed at eliminating or decreasing the latent reservoir. Progress in that direction has been hindered by the lack of biomarkers uniquely or differentially expressed on latently infected compared to their uninfected counterparts. To gain insight into the cellular mechanisms that take place in the context of latency, and with the goal of identifying distinctive markers that distinguish latently infected CD4+ T cells, we have used an in vitro model developed in our laboratory to study the expression profile of latently infected CD4+ T cells by microarray analysis. We have used a culture system, previously established in our laboratory, to generate and isolate quiescent latently infected CD4+ T cells in vitro. In this in vitro HIV-1 latency model, CD4+ T cells are activated, infected with full length, replication competent HIV-1, and then returned to quiescence in the presence of IL-7, yielding a culture of quiescent latently infected and uninfected cells. We showed that HIV-1 p24gag expressed during viral replication persists in the cytoplasm of latently infected cells for several days before being degraded. Therefore, we exploited the presence of cytoplasmic p24gag to sort latently infected from uninfected cells by FACS from the same initial cell culture. Total RNA was isolated from sorted latently infected and uninfected cells generated from CD4+ T cells of four different donors. Paired RNA samples from infected and uninfected cells were labeled with Cy3 and Cy5 to allow dual-color competitive hybridization. Moreover, to control for the dye bias in our experiments, we implemented a dye swap protocol (reciprocal labeling) for paired RNA samples from 2 donors. Samples were analyzed by dual-color competitive hybridization on the Agilent whole human genome microarrays (41,000 unique probes). This is the first comparative genomic profiling of primary latently infected resting memory CD4+ T cells versus their uninfected counterparts sorted from the same culture. Microarray analyses performed in this study revealed profound differences between latently infected and uninfected cells. Of relevance are genes involved, not only in previously described pathways related with transcriptional and post-transcriptional regulation, but affecting proliferation, survival, cell cycle progression and cell metabolism. This could explain why latently infected cells have been resistant to reactivation with current anti-latency approaches. Thus, targeting of more downstream steps, such as the ones identified in this study, may be able to enhance viral flushing from refractory latent reservoirs. In addition, we identified a panel of surface makers differentially expressed in latently infected cells, which seem worth investigating for their potential use as biomarkers. Indeed, they might allow the enrichment of this latent reservoir for molecular in depth studies, for monitoring the size of the latent reservoir in the clinical setting, as well as for the development of new therapeutic strategies aimed at eradicating this reservoir.
2013-03-15 | E-GEOD-40550 | biostudies-arrayexpress
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:HIV-1 latency is a major obstacle to achieve a functional cure for AIDS. To eradicate the viral reservoir, one of the strategies is to specifically reactivate HIV-1-infected cells and followed by elimination with potent immune surveillance. However, present latency-reversing agents (LRAs) are quite dissatisfactory because of their high toxicity and low efficiency. New targets need to be identified to develop more promising LRAs. Here, we found that histone chaperone chromatin assembly factor 1 (CAF-1) promotes HIV-1 latency by forming versatile suppressive nuclear bodies. CAF-1 plays a leading role for the formation of bodies recruiting multi-layer suppressive epigenetic modifiers and maintainers, and is of the characteristic of liquid-liquid phase separation (LLPS). Three distinct disordered regions of CHAF1A subunit coalesce CAF-1 body components by forming LLPS and play a key in maintaining HIV-1 latency. Therefore, disruptive induction of phase-separated CAF-1 body could be an important strategy to reactivate latent HIV-1.
2021-02-09 | PXD024172 |
Project description:Despite effective antiretroviral therapy at reducing HIV-1 viral loads to undetectable levels, the presence of latently infected CD4+ T cells poses a major barrier to HIV-1 cure. N6-methyladenosine (m6A) modification of viral and cellular RNA has a functional role in regulating HIV-1 infection. m6A modification of HIV-1 RNA can affect its stability, translation, and splicing in cells and suppresses type-I interferon induction in macrophages. However, the function of m6A modification in regulating HIV-1 latency reactivation remains unknown. We used the Jurkat T cell line-derived HIV-1 latency model (J-Lat cells) to investigate changes in m6A levels of cellular RNA in response to latency reversal. We observed a significant increase in m6A levels of total cellular RNA upon reactivation of latent HIV-1 in J-Lat cells. This increase in m6A levels was transient and returned to steady-state levels despite continued high levels of viral gene expression in reactivated cells compared to control cells. Upregulation of m6A levels occurred without significant changes in the protein expression of m6A writers or erasers that add or remove m6A, respectively. Knockdown of m6A writers in J-Lat cells significantly reduced HIV-1 reactivation. Treatment of a m6A writer inhibitor reduced cellular RNA m6A levels along with reduction in HIV-1 reactivation. Furthermore, using m6A-specific sequencing, we identified cellular RNAs that are differentially m6A-modified during HIV-1 reactivation in J-Lat cells. Knockdown of identified m6A-modified RNA validate these results with established primary CD4+ T-cell models of HIV-1 latency. These results showed the importance of m6A RNA modification in HIV-1 latency reversal.
2024-10-01 | GSE273614 | GEO
Project description:Investigation of whole genome gene expression level changes in HIV-1 latented infected cells, compared to the replicated cells and control cells. In this study, the in vitro steady cell culture was used to explore the mRNA transcription signatures in HIV-1 infection. mRNA profiles were performed and compared among normal control,HIV-1 latency and HIV-1 replication .
2012-12-01 | E-GEOD-38634 | biostudies-arrayexpress
Project description:HIV latency is a major obstacle to curing infection. Current strategies to eradicate HIV aim at increasing transcription of the latent provirus. In the present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed to produce viral particles upon ex vivo exposure to SAHA (vorinostat), despite effective inhibition of histone deacetylases. To identify steps that were not susceptible to the action of SAHA or other latency reverting agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing, and a viral-encoded reporter. This model served to investigate the characteristics of latently infected cells, the dynamics of HIV latency, and the process of reactivation induced by various stimuli. During latency, we observed persistence of viral transcripts but only limited viral translation. Similarly, the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data. This study highlights the importance of post-transcriptional blocks as one mechanism leading to HIV latency that needs to be relieved in order to purge the viral reservoir.
2017-02-24 | GSE95297 | GEO