title: Coordinated regulation of autophagy and apoptosis determines endothelial cell fate during Dengue virus type 2 infection.
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.
authors.affiliation: Key Laboratory of Tropical Diseases Control, Ministry of Education, Sun Yat-sen University, Guangzhou, 510275, China, huangjunqi1410@163.com.
authors.forename: Junqi
authors.initials: J
authors.lastname: Huang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yiming
authors.initials: Y
authors.lastname: Qi
authors.forename: Yingke
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Zilian
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuzhi
authors.initials: X
authors.lastname: Zhang
authors.forename: Lian
authors.initials: L
authors.lastname: Gui
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D002460:Cell Line; D003715:Dengue / Q000378:metabolism* / Q000473:pathology; D003716:Dengue Virus / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C468762:IFI6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C417551:XAF1 protein, human; D019014:fas Receptor