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IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells.

Qi Y, Li Y, Zhang Y, Zhang L, Wang Z, Zhang X, Gui L, Huang J - PLoS ONE (2015)

Bottom Line: Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects.We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells.By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China; Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, PR China.

ABSTRACT
Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) is a fatal infectious disease that demands an effective treatment. Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects. Among ISGs, IFN-α inducible gene 6 (IFI6) was increased in DENV infected human umbilical vascular endothelial cells (HUVECs) by microarray analysis in our previous study. However, its function is incompletely understood. In this study, we confirmed that IFI6 was markedly induced in DENV infection of both primary HUVECs and EA.hy926 cell lines. Recombinant EA.hy926 cell lines in which IFI6 was either over-expressed (IFI6+/+) or knocked-down (IFI6-/-) were generated. The activation of caspase-3 and intrinsic apoptosis-related protein caspase-9 were down-regulated in IFI6+/+ but up-regulated in IFI6-/- cells at 24-48 hrs post-infection. After incubation with DENV for 48 hrs, the mitochondrial membrane potential (Δψ(m)) was more stable in IFI6+/+ cells but reduced in IFI6-/- cells, as assayed by fluorescence staining with JC-1. We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells. By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells. It is presumed that the anti-apoptotic function of IFI6 is expressed by regulating the rheostatic balance between bcl-2/bax expression and inhibition of Δψ(m) depolarization during DENV infection of vascular endothelial cells(VECs). In addition, the pro-apoptotic protein X-linked Inhibitor of Apoptosis (XIAP)-Associated Factor 1(XAF1) expression had been reported to be up-regulated and led to the induction of apoptosis in DENV2-infected VECs,but the relationship between XAF1 and IFI6 dengue virus-induced apoptosis in VECs warrants further study.

No MeSH data available.


Related in: MedlinePlus

IFI6 influences the expressions of XAF1, bcl-2 and bax.(a) Recombinant cells were infected by DENV2 (MOI = 4) for 24, 36 and 48 hrs. Immunoblotting was used to detect the expression of XAF1, Bcl-2 and Bax in IFI6 over-expression or knock-down cell lines. (b) Quantitative data in panel a. The results shown were from three independent experiments.
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pone.0132743.g006: IFI6 influences the expressions of XAF1, bcl-2 and bax.(a) Recombinant cells were infected by DENV2 (MOI = 4) for 24, 36 and 48 hrs. Immunoblotting was used to detect the expression of XAF1, Bcl-2 and Bax in IFI6 over-expression or knock-down cell lines. (b) Quantitative data in panel a. The results shown were from three independent experiments.

Mentions: To verify whether the change in Δψm was associated with a balance in the expression of pro-apoptotic and anti-apototic proteins Bcl-2/Bax in the mitochondria or in other subcellular structures, we performed immunoblotting assays. The infected IFI6+/+ cells provoked a much higher level of Bcl-2, but a much lower level of Bax and the nuclear protein XAF1 as compared with the vector-high cells at the outset of virus challenge (Fig 6a). Additionally, Bcl-2 expression was lower in IFI6-/- cells, while expressions of Bax and XAF1 were both higher than those of vector-low cells at all time-points measured (Fig 6b).


IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue Virus 2 Infected Vascular Endothelial Cells.

Qi Y, Li Y, Zhang Y, Zhang L, Wang Z, Zhang X, Gui L, Huang J - PLoS ONE (2015)

IFI6 influences the expressions of XAF1, bcl-2 and bax.(a) Recombinant cells were infected by DENV2 (MOI = 4) for 24, 36 and 48 hrs. Immunoblotting was used to detect the expression of XAF1, Bcl-2 and Bax in IFI6 over-expression or knock-down cell lines. (b) Quantitative data in panel a. The results shown were from three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526556&req=5

pone.0132743.g006: IFI6 influences the expressions of XAF1, bcl-2 and bax.(a) Recombinant cells were infected by DENV2 (MOI = 4) for 24, 36 and 48 hrs. Immunoblotting was used to detect the expression of XAF1, Bcl-2 and Bax in IFI6 over-expression or knock-down cell lines. (b) Quantitative data in panel a. The results shown were from three independent experiments.
Mentions: To verify whether the change in Δψm was associated with a balance in the expression of pro-apoptotic and anti-apototic proteins Bcl-2/Bax in the mitochondria or in other subcellular structures, we performed immunoblotting assays. The infected IFI6+/+ cells provoked a much higher level of Bcl-2, but a much lower level of Bax and the nuclear protein XAF1 as compared with the vector-high cells at the outset of virus challenge (Fig 6a). Additionally, Bcl-2 expression was lower in IFI6-/- cells, while expressions of Bax and XAF1 were both higher than those of vector-low cells at all time-points measured (Fig 6b).

Bottom Line: Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects.We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells.By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells.

View Article: PubMed Central - PubMed

Affiliation: Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China; Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, PR China.

ABSTRACT
Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS) is a fatal infectious disease that demands an effective treatment. Interferon (IFN)-stimulated genes (ISGs) induced by dengue virus (DENV) exert antiviral effects. Among ISGs, IFN-α inducible gene 6 (IFI6) was increased in DENV infected human umbilical vascular endothelial cells (HUVECs) by microarray analysis in our previous study. However, its function is incompletely understood. In this study, we confirmed that IFI6 was markedly induced in DENV infection of both primary HUVECs and EA.hy926 cell lines. Recombinant EA.hy926 cell lines in which IFI6 was either over-expressed (IFI6+/+) or knocked-down (IFI6-/-) were generated. The activation of caspase-3 and intrinsic apoptosis-related protein caspase-9 were down-regulated in IFI6+/+ but up-regulated in IFI6-/- cells at 24-48 hrs post-infection. After incubation with DENV for 48 hrs, the mitochondrial membrane potential (Δψ(m)) was more stable in IFI6+/+ cells but reduced in IFI6-/- cells, as assayed by fluorescence staining with JC-1. We observed that Bcl-2 expression was increased in IFI6+/+ and decreased in IFI6-/- cells. By contrast, Bax expression was decreased in IFI6+/+ and increased in IFI6-/- cells. It is presumed that the anti-apoptotic function of IFI6 is expressed by regulating the rheostatic balance between bcl-2/bax expression and inhibition of Δψ(m) depolarization during DENV infection of vascular endothelial cells(VECs). In addition, the pro-apoptotic protein X-linked Inhibitor of Apoptosis (XIAP)-Associated Factor 1(XAF1) expression had been reported to be up-regulated and led to the induction of apoptosis in DENV2-infected VECs,but the relationship between XAF1 and IFI6 dengue virus-induced apoptosis in VECs warrants further study.

No MeSH data available.


Related in: MedlinePlus