Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 397, Issue 1-2, Pages 157-165Publisher
SPRINGER
DOI: 10.1007/s11010-014-2183-3
Keywords
Dengue virus; Autophagy; Apoptosis; Endothelial cells; XIAP-associated factor 1; Interferon-alpha-inducible protein 6
Categories
Funding
- National Natural Science Foundation of China [30872350, 31370870]
- Natural Science Foundation of Guangdong Province [s815100089 01000017, s2012010009050, s201302001300]
- Guangdong Province Scientific Technology Project [2010B050700008, 2011B040300022]
- Guangzhou City Scientific Technology Project [2011J4100084, 2008Z1-E221]
- Fundamental Research Funds for the Central Universities [10YKPY31]
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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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