Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand (Retracted article. See vol. 91, pg. 2658, 2010)
Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand (Retracted article. See vol. 91, pg. 2658, 2010)
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DOI：
10.1099/vir.0.80531-0
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Mori, N
中科院分区：
文献类型：
--
作者：
Matsuda, T;Almasan, A;Mori, N
虽然登革热出血热和登革热休克综合征的病例中有肝损伤的报道，但其机制仍然知之甚少。一些研究结果表明，登革病毒(DEN)可在体内诱导肝细胞凋亡。在这项工作中，DEN-2(DEN-2)株NGC可以诱导肝细胞系HepG2的凋亡，并且感染HepG2细胞可以诱导APO2配体(Apo2L，也称为肿瘤坏死因子相关的凋亡诱导配体或TRAIL)的表达。Apo2L/TRAIL诱导HepG2细胞凋亡，细胞表面表达Apo2L/TRAIL受体DR5/TRAIL-R2。对Apo2L/TRAIL启动子的分析表明，该基因被DEN-2感染激活，其反应元件是位于NT-75到-65的重叠的NF-B-K-和Sp1结合位点。蛋白酶体抑制剂N-乙酰-L-亮氨酰-L-亮氨酰-L去甲亮氨酸(LLNL)可抑制Apo2L/TRAIL基因的表达，LLNL和抗Apo2L/TRAIL抗体可抑制DEN-2诱导的细胞凋亡。有人认为，DEN感染促进细胞凋亡部分是通过诱导Apo2L/TRAIL的表达来实现的。
Although hepatic injury is reported in cases with dengue haemorrhagic fever and dengue shock syndrome, its mechanism remains poorly understood. Several findings suggest that dengue virus (DEN) induces apoptosis of hepatocytes in vivo. In this work, DEN type 2 (DEN-2) strain NGC was shown to induce apoptosis in the hepatic cell line HepG2, and infection of HepG2 cells was found to induce Apo2 ligand (Apo2L, also known as tumour necrosis factor-related apoptosis-inducing ligand or TRAIL) expression. Furthermore, Apo2L/TRAIL induced apoptosis in HepG2 cells, which expressed the Apo2L/TRAIL receptor DR5/TRAIL-R2 on their surface. Analysis of the Apo2L/TRAIL promoter revealed that this gene was activated by DEN-2 infection, whose responsive element was overlapping NF-B-K- and Sp1-binding sites located at nt-75 to -65. The proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL) inhibited Apo2L/TRAIL mRNA expression, and LLnL and anti-Apo2L/TRAIL antibody inhibited DEN-2-induced apoptosis. It was proposed that DEN infection promotes apoptosis partly through the induction of Apo2L/TRAIL expression.