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Homo sapiens

ABSTRACT: Transcriptome-wide analysis of the role of HTLV-1 Tax PBM in T-Cells from infected humanized-mice (hu-Mice)

PROVIDER: PRJNA397039 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5892703_1.fastq.gz	Fastqsanger.gz
	SRR5892703_2.fastq.gz	Fastqsanger.gz
	SRR5892704_1.fastq.gz	Fastqsanger.gz
	SRR5892704_2.fastq.gz	Fastqsanger.gz
	SRR5892705_1.fastq.gz	Fastqsanger.gz

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Transcriptome-wide analysis of the role of HTLV-1 Tax PBM in T-Cells from infected humanized-mice (hu-Mice)

Project description:Human T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization.

2018-02-14 | GSE102220 | GEO

KDR-dependent tyrosine phosphorylation in HTLV-1 transformed cells

Project description:Human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of adult T-cell leukemia (ATL) and the neuroinflammatory disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax oncoprotein regulates viral gene expression and the NF-kB pathway to promote the survival of HTLV-1 infected T cells. In thsi study, we utilize a kinome-wide shRNA screen to identify the tyrosine kinase KDR/VEGFR2 as an essential survival factor of HTLV-1-transformed T cells. Inhibition of KDR induces apoptosis of Tax expressing HTLV-1-transformed cell lines and CD4+ T cells from HAM/TSP patients. Phosphoproteomics analysis of HTLV-1 transformed cells treated with a KDR inhibitor revealed inhibition of the phosphorylation of multiple receptors/cell surface proteins, ubiquitin conjugating systems, proteases, phosphatases, apoptotic regulatory factors, adhesion/extracellular matrix proteins and viral proteins. This work suggests that HTLV-1 Tax has hijacked KDR kinase activity to promote Tax stability and the proliferation and survival of HTLV-1 infected cells.

2024-06-14 | PXD051981 | Pride

IL-27, PXN, CXCR4, GZMA, PRF1 and Foxp3 genes are differentially expressed in CD4+ T cells of HTLV-1-infected individuals.

2013-06-01 | GSE38537 | GEO

IL-27, PXN, CXCR4, GZMA, PRF1 and Foxp3 genes are differentially expressed in CD4+ T cells of HTLV-1-infected individuals.

Project description:HTLV-1 preferentially infects CD4+ T cells and these cells play a central role in HTLV-1 infection. In this study, we investigated the global gene expression profile of circulating CD4+ T cells from distinct clinical status of HTLV-1-infected individuals in regard to Tax expression levels. CD4+ T cells were isolated from asymptomatic HTLV-1 carrier (HAC) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, in order to identify genes involved in the HAM/TSP development. Hierarchical clustering analysis showed that healthy controls (CT) and HTLV-1-infected samples clustered separately. We also observed that HAC and HAM/TSP groups clustered separately regardless Tax expression. The gene expression profile of CD4+ T cells was compared among CT, HAC and HAM/TSP groups. The IL-27, PXN, CXCR4, GZMA, PRF1 and Foxp3 genes were differentially expressed between HAC and HAM/TSP groups and the frequency of CD4+Foxp3+ regulatory T cells (Treg) were higher in HTLV-1-infected individuals. These findings suggest that CD4+ T cells activity is distinct between HAC and HAM/TSP groups as expected. In order to study the transcriptional changes in CD4 T cell from HTLV-1-infected individuals, immunomagnetically purified CD4+ T-cells from the peripheral blood of 4 asymptomatic HTLV-1 carrier individuals (HAC) and 4 individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), as well as from 4 healthy controls (CT) were isolated and processed the microarray assay according Agilent's protocol. The differential expressed genes, molecular characterization and networks analysis were evaluated using robust bioinformatic tools, then the real time PCR was done to validate the genes.

2013-06-01 | E-GEOD-38537 | biostudies-arrayexpress

HTLV-1_hu_mice_RNA-Seq

Project description:RNA-seq analysis of cytoplasmic RNAs extracted from human T Cells obtained from humanized mice infected with wild-type HTLV-1 and a mutant form lacking the PBM of Tax.

| PRJEB22059 | ENA

Transcriptome analysis of HTLV-1 Tax-transformed T cell line Tesi in absence and presence of Tax

2008-02-14 | GSE10508 | GEO

RNA sequencing for transcriptome comparison between HTLV-1 Tax(-) and Tax(+) cells in Adult T-cell leukemia cell lines (MT-1 and KK-1)

Project description:Initially, ATL cell lines (MT-1 or KK-1) were stably transfected with reporter plasmid for HTLV-1 Tax expression, and single clones were isolated . This reporter in composed of Tax responsive element upstream of d2EGFP fluorescent protein. d2EGFP is expressed upon Tax expression in any individual cell. To compare transcriptomes of Tax(-) and Tax(+) cells, FACS sorting was done for d2EGFP(-) and d2EGFP(+) populations and RNA sequencing was performed.

2018-02-02 | GSE108601 | GEO

Identification of genes that are regulated by TAK1 in human cutaneous T cell lymphoma HuT-102 cells

Project description:We previously reported that human T cell lymphotropic virus 1 (HTLV-1) Tax oncoprotein constitutively activates TAK1. Here, we established Tax-positive HuT-102 cells stably downregulated TAK1 expression by short-hairpin RNA (HuT-shTAK1 cells), and investigated the physiological function of TAK1. Microarray analysis demonstrated that several interferon (IFN)-inducible genes including chemokines such as CXCL10 and CCL5 were significantly downregulated in HuT-shTAK1 cells. In contrast, Tax-mediated constitutive activation of NF-kB was intact in HuT-shTAK1 cells. IRF3, a critical transcription factor in innate immunity to viral infection, was constitutively activated in a Tax-dependent manner. Activation of IRF3 and IRF3-dependent gene expression were dependent on TAK1 and TBK1. On the other hand, IRF4, another IRF family of transcription factor overexpressed in a Tax-independent manner, negatively regulated the TAK1-dependent IRF3 transcriptional activity. Together, HTLV-1 manipulates IFN signaling by regulating both positive and negative IRFs.

2009-08-18 | GSE16219 | GEO

Transcription profiling of human CD4+ T-cell line Tesi in presence and absence of Tax

Project description:The Tesi system allows analysis of HTLV-1 Tax's impact on the transcriptome of a human CD4+ T-cell which is not derived from leukemia but directly from normal human lymphocytes. By comparing cells with and without Tax, one can specifically filter for celluar genes that are either activated or repressed in the presence of Tax. Experiment Overall Design: Tesi cells were kept in RPMI 1640 with 50% Panserin, 20% FCS, 0.35g/l glutamine, streptomycin as antibiotic and 40U/ml interleukin-2. To repress Tax expression, 1Âµg/ml tetracycline was added for ten days. Subsequently, total cellular RNA was extracted from samples and subjected to Affymetrix microarray analysis. For each state (with Tax and without Tax) a biological replicate was generated. Mean values of replicated samples were then compared.

2008-04-07 | E-GEOD-10508 | biostudies-arrayexpress

The viral oncoproteins Tax and HBZ control the host mRNA splicing landscape

Project description:We demonstrate that the HTLV-1 oncoviral proteins Tax and HBZ differentially alter the transcriptome landscape in T-cells

2021-09-13 | GSE146210 | GEO