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Coordinated regulation of autophagy and apoptosis determines endothelial cell fate during Dengue virus type 2 infection

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Abstract

Dengue is the most prevalent mosquito-borne viral disease in tropical regions. Severe cases may progress to Dengue hemorrhagic fever, suggesting vascular endothelial dysfunction in disease pathogenesis. In our previous study, we found that Dengue virus type 2 (DENV2) induced apoptosis of vascular endothelial cells via FasL/Fas- and XIAP-associated factor 1 (XAF1)-dependent pathways. In this paper, we demonstrate that DENV2 can induce autophagy in primary human umbilical vein endothelial cells (HUVECs) and the human umbilical vein endothelial cell line EA.hy926. Inhibition of autophagy with 3-methyl adenine promoted apoptosis, while inhibition of apoptosis with Z-VAD-FMK facilitated autophagy in DENV2-infected HUVECs and EA.hy926 cells. Interferon-alpha-inducible protein 6 (IFI6), a putative apoptosis regulator, inhibited DENV2-induced autophagy in EA.hy926 cells, while XAF1, an inhibitor of anti-apoptotic XIAP, facilitated autophagy. Molecular regulators of apoptosis and autophagy interact at multiple levels to determine cell fate. Our data suggest that XAF1 and IFI6 are involved in regulating the balance between autophagy and apoptosis in DENV2-infected endothelial cells.

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Acknowledgments

The present study was supported by National Natural Science Foundation of China (No.30872350 and No.31370870), Natural Science Foundation of Guangdong Province (No.s81510008901000017, No. s2012010009050 and No.s201302001300), Guangdong Province Scientific Technology Project (No. 2010B050700008 and No. 2011B040300022), Guangzhou City Scientific Technology Project (No. 2011J4100084 and No. 2008Z1-E221) and The Fundamental Research Funds for the Central Universities (No. 10YKPY31). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Institute of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510275, China

    Junqi Huang, Ying Li, Yiming Qi, Yingke Zhang, Lin Zhang, Xuzhi Zhang & Lian Gui

  2. Key Laboratory of Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510275, China

    Junqi Huang, Ying Li, Yiming Qi, Yingke Zhang, Lin Zhang, Xuzhi Zhang & Lian Gui

  3. First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China

    Zilian Wang

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  1. Junqi Huang
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Correspondence to Junqi Huang.

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Huang, J., Li, Y., Qi, Y. et al. Coordinated regulation of autophagy and apoptosis determines endothelial cell fate during Dengue virus type 2 infection. Mol Cell Biochem 397, 157–165 (2014). https://doi.org/10.1007/s11010-014-2183-3

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  • DOI: https://doi.org/10.1007/s11010-014-2183-3

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