Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA150111 | ENA |
REPOSITORIES: ENA
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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
Project description:Background: Interferon-alpha (IFN-a) contributes extensively to the host immune response upon viral infection through antiviral, pro-apoptotic, antiproliferative and immunomodulatory activities. Although extensively documented in various types of human cancers and viral infections, controversy exists in the exact mechanism of action of IFN-a in human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus type 1 (HTLV-1) retroviral infections. Principal Findings: IFN-a displayed robust anti-HIV-1 effects in HTLV-1/HIV-1 co-infected MT-4 cells in vitro, demonstrated by the dose-dependent inhibition of the HIV-1-induced cytopathic effect (IC50 = 83.5IU/ml, p < 0.0001) and p24 secretion (IC50 = 1.2 IU/ml, p < 0.0001). In contrast, IFN-a treatment did not affect cell viability nor HTLV-1 viral RNA levels in HTLV-1 mono-infected cell lines, based on flow cytometry and nCounter analysis. However, we were able to confirm the previously described posttranscriptional inhibition of HTLV-1 p19 secretion by IFN-a, both in cell lines (p = 0.0045) as well as in adult T cell leukemia patient samples (p = 0.031). In addition, through microarray and nCounter analysis, we demonstrated significant transcriptional activation of interferon-stimulated genes and intact IFN-a signaling in HTLV-1-infected cell lines. Conclusions: Taken together, our results indicate that both the absence of in vitro antiproliferative and pro-apoptotic activity, as well as the modest posttranscriptional antiviral activity of IFN-a against HTLV-1, was not due to a cell intrinsic defect in IFN-a signalisation, but rather represents a retrovirus-specific phenomenon, considering the robust HIV-1 inhibition in co-infected cells.
2015-01-01 | GSE34870 | GEO
Project description:To address whether changes in miRNA expression accompany cell-associated replication of HTLV-1 in vivo, we carried out the miRNA expression profiling of CD4+ and CD8+ T-cells derived from naturally HTLV-1 infected individuals with no clinical sign of malignancy. T-cell clones were obtained by limiting dilution culture of PBMCs of HTLV-1 carriers. miRNA expression was assessed by Agilent V3 miRNA array according to the manufacturer's instructions. miRNA expression profiles of cloned CD4+ and CD8+ T-cells (carrying or not HTLV-1) derived from naturally HTLV-1 infected individuals.
2014-12-03 | E-GEOD-46345 | biostudies-arrayexpress
Project description:Human tumor cell lines treated with interferon-alpha-2a
| PRJNA126607 | ENA
Project description:MicroRNA expression profiling in human tumor cell lines treated with interferon-alpha-2a
| PRJNA116363 | ENA
Project description:To address whether changes in miRNA expression accompany cell-associated replication of HTLV-1 in vivo, we carried out the miRNA expression profiling of CD4+ and CD8+ T-cells derived from naturally HTLV-1 infected individuals with no clinical sign of malignancy. T-cell clones were obtained by limiting dilution culture of PBMCs of HTLV-1 carriers. miRNA expression was assessed by Agilent V3 miRNA array according to the manufacturer's instructions.
2014-12-03 | GSE46345 | GEO
Project description:Expression data from CD4-positive HTLV-positive cell lines and from CD4-positive HTLV-negative primary cells.
| PRJNA118429 | ENA
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
Project description:Whole genome sequencing of HTLV-1-infected cell lines
| PRJDB11215 | ENA
Project description:HTLV-1 infected individuals stay as carriers for their lifetimes, while the rest of 5% are killed by ATL. ATL leukemogenesis is a complex process involving accumulation of multiple genetic abnormalities in HTLV-1 infected cells. To clarify genetic events underlying ATL leukemogenesis, we conducted comprehensive miRNA expression profiling in 40 ATL patients and in 22 healthy volunteers. Total RNA samples from PBMC of ATL patients (mostly HTLV-1 inefcted CD4+ T-cells) and from CD4+ T-cells from healthy donors were subjected to Cy-3 labeling followed by miRNA expression microarray analyses.
2012-02-23 | E-GEOD-31629 | biostudies-arrayexpress