Investigation of temporal changes in cellular gene expression upon infection with HIV-1.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE56484 | GEO | 2014/05/02
SECONDARY ACCESSION(S): PRJNA243418
REPOSITORIES: GEO
Similar Datasets
Project description:The purpose was to study temporal changes in cellular gene expression upon infection with HIV-1. The T lymphoblastic leukemia cell line SUP-T1 was infected with HIV-1 The purpose was to study temporal changes in cellular gene expression upon infection with HIV-1. 1x10^6 homo sapien were infected with LAI/lab strain at MOI giving infection of almost 100% of cells; this was visible in a QC step in which cells 24 hours after infection were stained for p24 antigen. MOI was set so that this infection rate was achieved after 1 hour incubation of cells with virus. Mock, UV-inactivated virus, and live virus infections were carried out in three (each) separate tubes and infected cells were maintained in separate suspensions (9 samples each). Time point aliquots were then collected in 4-hr intervals from each suspension, cells were pelleted, and lysed in 1 ml Trizol. Lysed samples were immediately frozen on dry ice and moved to -80M-BM-0C until RNA extraction, probe labeling and microarray analysis.
2014-05-02 | E-GEOD-56484 | biostudies-arrayexpress
Project description:Expression analysis was performed with human SUP-T1 cell line infected with HIV alone, treated with curcumin alone and infected with HIV in presence of curcumin. The control untreated sample was compared with all the three types of treatments to calculate the fold change. The purpose of the experiment was to identify set of genes that are dys-regulated during HIV infection and shows normal expression when treated with curcumin. This experiment is useful in identifying the mechanism of anti-HIV activity of curcumin at genetic level.
2015-10-29 | E-MTAB-3977 | biostudies-arrayexpress
Project description:HIV accessory proteins manipulate host factors to evade cellular restriction and enhance viral replication. We used multiplex tandem mass tag (TMT)-based whole cell proteomics to gain a comprehensive, time-based overview of proteins and processes subverted during HIV infection. To make specific functional and mechanistic predictions and systematically identify candidate accessory protein targets, we categorized cellular proteins regulated by HIV according to their patterns of temporal expression. As well as depleting APOBEC family members, we found Vif to be necessary and sufficient for CUL5-dependent degradation of all members of the B56 family of regulatory subunits of the key cellular phosphatase PP2A. Quantitative phosphoproteomic analysis of HIV-infected cells confirmed Vif-dependent hyperphosphorylation of >200 cellular proteins, particularly substrates of the aurora kinases. The ability of Vif to target PP2A subunits spans primate and non-primate lentiviral lineages, and remodeling of the cellular phosphoproteome is therefore a second ancient and conserved Vif function.
2016-09-29 | PXD004187 | Pride
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: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:Copy Number Variaton (CNV) detection of human BCR-ABL positive acute lymphoblastic leukemia (ALL) cell line, SUP-B15.
2023-07-29 | GSE239416 | GEO
Project description:The human immunodeficiency virus (HIV-1) is highly dependent on a variety of host factors. Beside proteins, host RNA molecules have been reported to aid HIV-1 replication and latency maintenance. Here we report the use of multiple workflows of native RNA immunoprecipitation and sequencing (nRIPseq) to determine direct host RNA interaction partners of all 18 HIV-1 (poly)proteins. We identified 1,727 HIV-1 protein – human RNA interactions in the Jurkat cell line and 1,558 interactions in SupT1 cells for a subset of proteins. We discovered different cellular pathways that seem to be used or controlled by HIV-1 on the RNA level: Tat binds for example mRNAs of proteins involved in the super elongation complex (AFF1-4, Cyclin-T1). Correlation of the interaction scores (based on binding abundancy) allowed to identify the highest confidence interactions, for which we performed a small-scale knockdown screen that led to the identification of three HIV-1 protein binding RNA interactors involved in HIV-1 replication (AFF2, H4C9 and RPLP0).
2024-07-31 | GSE268788 | GEO
Project description:Genome wide DNA methylation profiles of various human brain regions (cerebellum, occipital lobe, etc). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. The dataset includes 130 samples. Multiple brain regions were assessed per subject. The goal was to evaluate the effect of HIV infection on DNA methylation levels. Genome wide DNA methylation profiles of various brain regions from HIV positive and negative subjects. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. Dataset included 130 samples: 99 samples from HIV+ subjects and 31 samples from HIV- subjects. The Illumina Infinium450 platform was applied to various brain regions from HIV+ and HIV- subjects. We evaluated 130 brain samples from 84 different subjects. Specifically, we considered cerebellum (20 HIV+ samples and 4 controls), frontal lobe (2 cases, 4 controls), hippocampus (4 controls), medial frontal cortex (18 cases), occipital cortex (59 cases, 13 controls), temporal cortex (4 controls). In total, there were 99 samples from HIV+ subjects and 31 samples from HIV- controls of similar ages. The subjects were recruited from the National Neurological AIDS Bank study or Multicenter AIDS Cohort study in Los Angeles. Informed consent and all study procedures were approved by the UCLA Medical IRB. DNAm data from HIV+ cases and HIV- controls were generated at the same time and randomized across plates and chips. HIV viral load information was available for blood (measured at the last blood draw) and for cerebrospinal fluid (CSF).
2015-06-09 | E-GEOD-59457 | biostudies-arrayexpress
Project description:Cyclin T1-dependent genes in LPS-activated MM6 cells. HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up-regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that are Cyclin T1-dependent for their induction in activated CD4+ T cells and during macrophage differentiation and activation. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value < 0.00021). SiRNA depletions of two CTDGs identified here, CDK11 and Casein kinase1gamma1, suggest that these genes are also involved in HIV-1 replication. It is therefore likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors. Keywords: cyclin T1 knockdown
2008-07-31 | GSE10738 | GEO