Genome-wide analysis of gene expression profiles in individuals infected with the Human T-Lymphotropic virus Type 1 (HTLV-1) - test set
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29332 | GEO | 2012/01/01
SECONDARY ACCESSION(S): PRJNA142809
REPOSITORIES: GEO
Similar Datasets
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects. Patients attending the HTLV-1 clinic at St Mary’s hospital in London, UK were classified according to their clinical status as asymptomatic HTLV-1 carriers (ACs, n=17), patients with HTLV-1-associated meylopathy (HAM, n=10) or uninfected control subjects (n=8). Three ml of blood were drawn into a Tempus tube (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted, globin mRNA depleted and following cRNA generation samples were analysed on HUmanWG6 v3 Illumina BeadChip arrays.
2012-01-01 | E-GEOD-29332 | biostudies-arrayexpress
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis.
2012-01-01 | GSE29312 | GEO
Project description:Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis. Patients attending the HTLV-1 clinic at St Mary’s hospital in London, UK were classified according to their clinical status as asymptomatic HTLV-1 carriers (ACs, n=20), patients with HTLV-1-associated meylopathy (HAM, n=10) or uninfected control subjects (n=9). HTLV-1 proviral load (PVL) can differ among individuals by more than 10-fold and is typically higher in patients with HAM than in ACs, with a 1% PVL cut off generally separating disease from asymptomatic carriage. Thus, ACs were subdivided into AC low PVL (<1% infected PBMCs) and AC high PVL (>1% infected PBMCs). Three ml of blood were drawn into a Tempus tube (Applied Biosystems, Foster City, CA, USA). Total RNA was extracted, globin mRNA depleted and following cRNA generation samples were analysed on HUmanHT12 v3 Illumina BeadChip arrays.
2012-01-01 | E-GEOD-29312 | biostudies-arrayexpress
Project description:HTLV-1 is the etiologic agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE to assess gene expression profiles of CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients, in order to identify genes involved in the HAM/TSP development. Analysis of SAGE was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between controls and HAC or HAM/TSP identified around 900 genes. HAC versus HAM/TSP libraries showed 285 differentially expressed genes. We found that CXCR4 had a lower expression level in the HTLV-1 infected group than in controls. CCL5 had higher expression in HAM/TSP group, as compared to HAC. Our results provide a large-scale perspective of gene expression that may be further tested with functional assays to increase our understanding on the HTLV1-related diseases pathology. Comparative analysis of gene expression profiles of CD8+ T Lymphocytes isolated from HTLV-1 infected individuals.
2013-05-08 | E-GEOD-26150 | biostudies-arrayexpress
Project description:Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory neurodegenerative disease that affects motor, urinary, intestinal, and sensory functions. Typically, HAM/TSP is slowly progressive, but it may vary from limited motor disability after decades (very slow progression) to loss of motor function in a few years from disease onset (rapid). In this study, we aimed to identify prognostic biomarkers for HAM/TSP to support patient management. Thus, proteomic analysis of the cerebrospinal fluid (CSF) was performed with samples from HTLV-1 asymptomatic carriers (AC) (n=13) and HAM/TSP patients (n=21) with rapid, typical, and very slow progression using quantitative label-free liquid chromatography/tandem mass spectrometry. Enrichment analyses were also carried out to identify key biological processes associated with distinct neurological conditions in HTLV-1 infection. Candidate biomarkers were validated by ELISA in paired CSF and serum samples, and samples from HTLV-1-seronegative individuals (n=9) were used as controls. CSF analysis identified 602 proteins. Leukocyte/cell activation, immune response processes and neurodegeneration pathways were enriched in rapid progressors. Conversely, HTLV-1 AC and HAM/TSP patients with typical and very slow progression had enriched processes for nervous system development. Differential expression analysis showed that soluble vascular cell adhesion molecule 1 (sVCAM-1), chitotriosidase 1 (CHIT1), and cathepsin C (CTSC) were upregulated in HAM/TSP. However, only CHIT1 was significantly elevated after validation, particularly in HAM/TSP rapid progressors. In contrast, none of these biomarkers were altered in serum. Additionally, CSF CHIT1 levels in HAM/TSP patients positively correlated with the speed of HAM/TSP progression, defined as points in the IPEC-2 HAM/TSP disability scale per year of disease, and with CSF levels of phosphorylated neurofilament heavy chain, neopterin, CXCL5, CXCL10, and CXCL11. In conclusion, higher CSF levels of CHIT1 were associated with HAM/TSP rapid progression and correlated with other biomarkers of neuroinflammation and neurodegeneration. Therefore, we propose CHIT1 as a surrogate CSF biomarker to identify HAM/TSP patients with a worse prognosis.
2022-07-27 | PXD034065 | Pride
Project description:HTLV-1 is the etiologic agent of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD8+ T cells may contribute to the protection or development of HAM/TSP. In this study we used SAGE to assess gene expression profiles of CD8+ T cells isolated from HTLV-1 asymptomatic carriers (HAC) and from HAM/TSP patients, in order to identify genes involved in the HAM/TSP development. Analysis of SAGE was conducted by pooling samples according to clinical status. The comparison of gene expression profiles between controls and HAC or HAM/TSP identified around 900 genes. HAC versus HAM/TSP libraries showed 285 differentially expressed genes. We found that CXCR4 had a lower expression level in the HTLV-1 infected group than in controls. CCL5 had higher expression in HAM/TSP group, as compared to HAC. Our results provide a large-scale perspective of gene expression that may be further tested with functional assays to increase our understanding on the HTLV1-related diseases pathology.
2013-05-08 | GSE26150 | GEO
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:Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles played by cellular genes in HTLV-1-infected CD4+ T cells await discovery. We combined microarray data and pathway analysis, and found that the ABL1 tyrosine kinase gene is a critical gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes. ABL1 is also part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML), and tyrosine kinase inhibitors (TKI), including imatinib, nilotinib, and dasatinib, are in safe clinical use for treating CML. To evaluate whether ABL1 is indeed critical for the pathogenesis of HAM/TSP, we investigated the effect of ABL1 inhibitors on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and DNA from dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKI. Treating the PBMCs with nilotinib or dasatinib produced significant reductions in the PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, a retrospective survey based on our clinical records found a rare case of HAM/TSP, where the patient also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is a significant gene for the survival of HTLV-1-infected cells and that TKI may be a potential therapeutic agent for HAM/TSP.
2020-05-26 | GSE132666 | GEO
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.
2013-06-01 | GSE38537 | GEO
Project description:We examined the gene expression profiles of CD4+ T-cells isolated from 7 ATL, 12 HAM/TSP and 11 AC (asymptomatic carriers) to identify gene signatures that may be characteristic for these particular diseases. Using gene expression arrays, we identified ~ 1039 immune-related genes that were differentially expressed in CD4+ T cells; using stringent exclusion criteria, a 122 gene signature could be divided into 3 groups: I) ATL-specific; II) common; and III) HAM/TSP-specific markers To better understand the genetic differences between HTLV-1-associated diseases, we examined the gene expression profile of T lymphocytes from patients either suffering from ATL, HAM/TSP or carrying the HTLV-1 virus without any symptoms. Microarray experiments were performed using the human ImmuneArray cDNA array (UHN Microarray Center, University of Toronto). We used the Stratagene Universal Control, labelled Cy5 for all samples in a competitive hybridization.
2010-02-13 | E-GEOD-19080 | biostudies-arrayexpress