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Molecular profiling of T-helper immune genes during dengue virus infection.

Chen J, Ng MM, Chu JJ - Virol. J. (2008)

Bottom Line: Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability.Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability.Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, 5 Science Drive 2, National University of Singapore, 117597 Singapore. g0800060@nus.edu.sg

ABSTRACT
In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome.

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Expression and statistical validation profiles of Th genes in dengue virus infected Jurkat cells. The differential regulation (up or down-regulated) of the 84 Th and Th-related genes upon dengue virus infection of Jurkat cells are shown. Genes with greater than 3Log2 fold increase are indicated in the respective graphs of each cell types. The volcano plot of the RT-PCR array for each of the cell types is also provided. The plot arranges Th genes along dimensions of differential regulation (either up or down-regulation – X axis) and statistical significance (Y-axis). The higher values on the Y-axis indicate statistical significant of the up or down-regulated genes.
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Figure 2: Expression and statistical validation profiles of Th genes in dengue virus infected Jurkat cells. The differential regulation (up or down-regulated) of the 84 Th and Th-related genes upon dengue virus infection of Jurkat cells are shown. Genes with greater than 3Log2 fold increase are indicated in the respective graphs of each cell types. The volcano plot of the RT-PCR array for each of the cell types is also provided. The plot arranges Th genes along dimensions of differential regulation (either up or down-regulation – X axis) and statistical significance (Y-axis). The higher values on the Y-axis indicate statistical significant of the up or down-regulated genes.

Mentions: Genes with fold value more than 2 in absolute value were considered to be differentially regulated. P-value of 3 independent control experiments and test experiments obtained for each gene was calculated. The differential regulation of the Th genes upon DENV infection of the human cell types are tabulated in Tables 2, 3 and 4. The Th genes are further classified based on their potential pathogenesis-induced classes (immune cell activation, inflammation, thrombocytopenia and vascular permeability) with reference to the description of the gene function summarized from Online Mendelian Inheritance in Man (OMIM), National Center for Biotechnology Information, National Library of Medicine as of November 2008. From these genes, a group of 20 genes that may provide the molecular basis of the observed pathogenesis in the human cells upon DENV infection was identified (Tables 2, 3 and 4 – bolded). The criterion for the selection of these genes was based on their ability to enhance immune cell activation, inflammatory responses, thrombocytopenia as well as vascular permeability upon differential regulation. The complete gene expression profiles of all the three cell lines infected with DENV were provided (Figures 2, 3 and 4). The Th genes that were either up or down-regulated significantly in the different cell types were also indicated in the volcano plots as shown in Figures 2, 3 and 4. RANTES, CC-CKR-3, TLR6 and IL-6 were highly up-regulated in Jurkat and K562 cells upon infection with dengue virus. CD40L was shown to be significantly down-regulated in both Jurkat and HepG2 cells upon dengue virus infection.


Molecular profiling of T-helper immune genes during dengue virus infection.

Chen J, Ng MM, Chu JJ - Virol. J. (2008)

Expression and statistical validation profiles of Th genes in dengue virus infected Jurkat cells. The differential regulation (up or down-regulated) of the 84 Th and Th-related genes upon dengue virus infection of Jurkat cells are shown. Genes with greater than 3Log2 fold increase are indicated in the respective graphs of each cell types. The volcano plot of the RT-PCR array for each of the cell types is also provided. The plot arranges Th genes along dimensions of differential regulation (either up or down-regulation – X axis) and statistical significance (Y-axis). The higher values on the Y-axis indicate statistical significant of the up or down-regulated genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2628356&req=5

Figure 2: Expression and statistical validation profiles of Th genes in dengue virus infected Jurkat cells. The differential regulation (up or down-regulated) of the 84 Th and Th-related genes upon dengue virus infection of Jurkat cells are shown. Genes with greater than 3Log2 fold increase are indicated in the respective graphs of each cell types. The volcano plot of the RT-PCR array for each of the cell types is also provided. The plot arranges Th genes along dimensions of differential regulation (either up or down-regulation – X axis) and statistical significance (Y-axis). The higher values on the Y-axis indicate statistical significant of the up or down-regulated genes.
Mentions: Genes with fold value more than 2 in absolute value were considered to be differentially regulated. P-value of 3 independent control experiments and test experiments obtained for each gene was calculated. The differential regulation of the Th genes upon DENV infection of the human cell types are tabulated in Tables 2, 3 and 4. The Th genes are further classified based on their potential pathogenesis-induced classes (immune cell activation, inflammation, thrombocytopenia and vascular permeability) with reference to the description of the gene function summarized from Online Mendelian Inheritance in Man (OMIM), National Center for Biotechnology Information, National Library of Medicine as of November 2008. From these genes, a group of 20 genes that may provide the molecular basis of the observed pathogenesis in the human cells upon DENV infection was identified (Tables 2, 3 and 4 – bolded). The criterion for the selection of these genes was based on their ability to enhance immune cell activation, inflammatory responses, thrombocytopenia as well as vascular permeability upon differential regulation. The complete gene expression profiles of all the three cell lines infected with DENV were provided (Figures 2, 3 and 4). The Th genes that were either up or down-regulated significantly in the different cell types were also indicated in the volcano plots as shown in Figures 2, 3 and 4. RANTES, CC-CKR-3, TLR6 and IL-6 were highly up-regulated in Jurkat and K562 cells upon infection with dengue virus. CD40L was shown to be significantly down-regulated in both Jurkat and HepG2 cells upon dengue virus infection.

Bottom Line: Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability.Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability.Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, 5 Science Drive 2, National University of Singapore, 117597 Singapore. g0800060@nus.edu.sg

ABSTRACT
In this study, we provide a comprehensive molecular profiling of the involvement of T- helper (Th) genes during dengue virus infection of different cell types. The Th gene profiles of three human cell types (monocytes, T-cells and hepatocytes) were analyzed simultaneously via array-based RT-PCR upon infection with dengue virus. Differential regulation of 41 Th genes was identified and of which 20 of those genes may contribute to immuno-pathogenesis of dengue virus infection by regulating inflammation, thrombocytopenia and vascular permeability. Among the strongly up-regulated genes were the RANTES, CC-CKR3, IRF4, CLEC2C, IL-6 and TLR6, which are potent inducer of inflammation and vascular permeability. Profiling genes obtained from this study may serve as potential biomarkers and the modulation of Th immune responses during dengue virus infection has important implications in disease outcome.

Show MeSH
Related in: MedlinePlus