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The transcription profile of Tax-3 is more similar to Tax-1 than Tax-2: insights into HTLV-3 potential leukemogenic properties.

Chevalier SA, Durand S, Dasgupta A, Radonovich M, Cimarelli A, Brady JN, Mahieux R, Pise-Masison CA - PLoS ONE (2012)

Bottom Line: These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation.The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation.In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and suggest that HTLV-3 might share pathogenic features with HTLV-1 in vivo.

View Article: PubMed Central - PubMed

Affiliation: Virus Tumor Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. sebastien.chevalier@ens-lyon.fr

ABSTRACT
Human T-cell Lymphotropic Viruses type 1 (HTLV-1) is the etiological agent of Adult T-cell Leukemia/Lymphoma. Although associated with lymphocytosis, HTLV-2 infection is not associated with any malignant hematological disease. Similarly, no infection-related symptom has been detected in HTLV-3-infected individuals studied so far. Differences in individual Tax transcriptional activity might account for these distinct physiopathological outcomes. Tax-1 and Tax-3 possess a PDZ binding motif in their sequence. Interestingly, this motif, which is critical for Tax-1 transforming activity, is absent from Tax-2. We used the DNA microarray technology to analyze and compare the global gene expression profiles of different T- and non T-cell types expressing Tax-1, Tax-2 or Tax-3 viral transactivators. In a T-cell line, this analysis allowed us to identify 48 genes whose expression is commonly affected by all Tax proteins and are hence characteristic of the HTLV infection, independently of the virus type. Importantly, we also identified a subset of genes (n = 70) which are specifically up-regulated by Tax-1 and Tax-3, while Tax-1 and Tax-2 shared only 1 gene and Tax-2 and Tax-3 shared 8 genes. These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation. Analysis of the molecular interactions existing between those Tax-1/Tax-3 deregulated genes then allowed us to highlight biological networks of genes characteristic of HTLV-1 and HTLV-3 infection. The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation. In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and suggest that HTLV-3 might share pathogenic features with HTLV-1 in vivo.

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Related in: MedlinePlus

Functional analysis of 70 cellular genes deregulated only in Tax-1 and Tax-3 transduced cells.Schematic representation of the 70 cellular genes implicated in molecular interactions, using the STRING software. Width of the lines reflects the score of molecular interaction and the circles are colored according to the GO Biological Process association. The color legend is indicated in the table below the network. Each color represents the main GO terms associated with genes composing the network, identified by BINGO analysis (Hypergeometric test and Benjamini & Hochberg False Discovery Rate (FDR) correction; significance level <0.05).
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pone-0041003-g014: Functional analysis of 70 cellular genes deregulated only in Tax-1 and Tax-3 transduced cells.Schematic representation of the 70 cellular genes implicated in molecular interactions, using the STRING software. Width of the lines reflects the score of molecular interaction and the circles are colored according to the GO Biological Process association. The color legend is indicated in the table below the network. Each color represents the main GO terms associated with genes composing the network, identified by BINGO analysis (Hypergeometric test and Benjamini & Hochberg False Discovery Rate (FDR) correction; significance level <0.05).

Mentions: Molecular interactions existing between the 70 genes composing the molecular signature specific to Tax-1 and Tax-3 were further examined as a biological network (Figure 14). The majority of the genes are functionally linked in biological processes characteristic of Tax-1 expressing HTLV-1 infected T-cells: regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation.


The transcription profile of Tax-3 is more similar to Tax-1 than Tax-2: insights into HTLV-3 potential leukemogenic properties.

Chevalier SA, Durand S, Dasgupta A, Radonovich M, Cimarelli A, Brady JN, Mahieux R, Pise-Masison CA - PLoS ONE (2012)

Functional analysis of 70 cellular genes deregulated only in Tax-1 and Tax-3 transduced cells.Schematic representation of the 70 cellular genes implicated in molecular interactions, using the STRING software. Width of the lines reflects the score of molecular interaction and the circles are colored according to the GO Biological Process association. The color legend is indicated in the table below the network. Each color represents the main GO terms associated with genes composing the network, identified by BINGO analysis (Hypergeometric test and Benjamini & Hochberg False Discovery Rate (FDR) correction; significance level <0.05).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3401231&req=5

pone-0041003-g014: Functional analysis of 70 cellular genes deregulated only in Tax-1 and Tax-3 transduced cells.Schematic representation of the 70 cellular genes implicated in molecular interactions, using the STRING software. Width of the lines reflects the score of molecular interaction and the circles are colored according to the GO Biological Process association. The color legend is indicated in the table below the network. Each color represents the main GO terms associated with genes composing the network, identified by BINGO analysis (Hypergeometric test and Benjamini & Hochberg False Discovery Rate (FDR) correction; significance level <0.05).
Mentions: Molecular interactions existing between the 70 genes composing the molecular signature specific to Tax-1 and Tax-3 were further examined as a biological network (Figure 14). The majority of the genes are functionally linked in biological processes characteristic of Tax-1 expressing HTLV-1 infected T-cells: regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation.

Bottom Line: These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation.The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation.In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and suggest that HTLV-3 might share pathogenic features with HTLV-1 in vivo.

View Article: PubMed Central - PubMed

Affiliation: Virus Tumor Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America. sebastien.chevalier@ens-lyon.fr

ABSTRACT
Human T-cell Lymphotropic Viruses type 1 (HTLV-1) is the etiological agent of Adult T-cell Leukemia/Lymphoma. Although associated with lymphocytosis, HTLV-2 infection is not associated with any malignant hematological disease. Similarly, no infection-related symptom has been detected in HTLV-3-infected individuals studied so far. Differences in individual Tax transcriptional activity might account for these distinct physiopathological outcomes. Tax-1 and Tax-3 possess a PDZ binding motif in their sequence. Interestingly, this motif, which is critical for Tax-1 transforming activity, is absent from Tax-2. We used the DNA microarray technology to analyze and compare the global gene expression profiles of different T- and non T-cell types expressing Tax-1, Tax-2 or Tax-3 viral transactivators. In a T-cell line, this analysis allowed us to identify 48 genes whose expression is commonly affected by all Tax proteins and are hence characteristic of the HTLV infection, independently of the virus type. Importantly, we also identified a subset of genes (n = 70) which are specifically up-regulated by Tax-1 and Tax-3, while Tax-1 and Tax-2 shared only 1 gene and Tax-2 and Tax-3 shared 8 genes. These results demonstrate that Tax-3 and Tax-1 are closely related in terms of cellular gene deregulation. Analysis of the molecular interactions existing between those Tax-1/Tax-3 deregulated genes then allowed us to highlight biological networks of genes characteristic of HTLV-1 and HTLV-3 infection. The majority of those up-regulated genes are functionally linked in biological processes characteristic of HTLV-1-infected T-cells expressing Tax such as regulation of transcription and apoptosis, activation of the NF-κB cascade, T-cell mediated immunity and induction of cell proliferation and differentiation. In conclusion, our results demonstrate for the first time that, in T- and non T-cells types, Tax-3 is a functional analogue of Tax-1 in terms of transcriptional activation and suggest that HTLV-3 might share pathogenic features with HTLV-1 in vivo.

Show MeSH
Related in: MedlinePlus