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http://asiair.asia.edu.tw/ir/handle/310904400/111675
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| Title: | Anti-apoptotic activity of Japanese encephalitis virus NS5 protein in human medulloblastoma cells treated with interferon-β |
| Authors: | Weng, Jing-Ru;Weng, Jing-Ru;Hu, Chun-Hung;Hua, Chun-Hung;Chao-Hsien, Chao-Hsien C;Chen, Chao-Hsien;黃素華;Huang, Su-Hua;林振文 |
| Contributors: | 生物科技學系 |
| Date: | 2018-08 |
| Issue Date: | 2018-12-25 02:31:36 (UTC+0) |
| Abstract: | Background
Japanese encephalitis virus (JEV) non-structural protein 5 (NS5) exhibits type I interferon (IFN) antagonists, contributing to immune escape, and even inducing viral anti-apoptosis. This study investigated the anti-apoptotic mechanism of JEV NS5 protein on type I IFN-induced apoptosis of human medulloblastoma cells.
Methods
Vector control and NS5-expressing cells were treated with IFN-β, and then harvested for analyzing apoptotic pathways with flow cytometry, Western blotting, subcellular localization, etc.
Results
Annexin V-FITC/PI staining indicated that IFN-β triggered apoptosis of human medulloblastoma cells, but JEV NS5 protein significantly inhibited IFN-β-induced apoptosis. Phage display technology and co-immunoprecipitation assay identified the anti-apoptotic protein Hsp70 as a NS5-interacting protein. In addition, Western blotting demonstrated that NS5 protein up-regulated the Hsp70 expression, and reduced IFN-β-induced phosphorylation of ERK2, p38 MAPK and STAT1. Hsp70 down-regulation by quercetin significantly recovered IFN-β-induced apoptosis of NS5-expressing cells, correlating with the increase in the phosphorylation of ERK2, p38 MAPK, and STAT1. Inhibiting the ATPase activity of Hsp70 by VER-155008 resulted in the elevated IFN-β-induced apoptosis in vector control and NS5-expressing cells.
Conclusions
The results indicated Hsp70 up-regulation by JEV NS5 not only involved in type I IFN antagonism, but also responded to the anti-apoptotic action of JEV NS5 protein through the blocking IFN-β-induced p38 MAPK/STAT1-mediated apoptosis. |
| Relation: | Journal of Microbiology, Immunology and Infection |
| Appears in Collections: | [生物科技學系] 期刊論文
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