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標題: Japanese encephalitis virus infection activates caspase-8 and-9 in a FADD-independent and mitochondrion-dependent manner
作者: 蘇鴻麟
Tsao, C.H.
Su, H.L.
Lin, Y.L.
Yu, H.P.
Kuo, S.M.
Shen, C.I.
Chen, C.W.
Liao, C.L.
關鍵字: reovirus-induced apoptosis;programmed cell-death;induce apoptosis;permeability transition;endoplasmic-reticulum;cultured-cells;human;bcl-2;t-cells;pathway;expression
Project: Journal of General Virology
期刊/報告no:: Journal of General Virology, Volume 89, Page(s) 1930-1941.
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, replicates primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected cells. This study investigated the hierarchical activation of the caspase network induced by JEV infection. It was found that JEV activated the initiators caspase-8 and -9, as well as effector caspase-3, in infected baby hamster kidney and mouse neuroblastoma (N 18) cells. In neuronal N 18 cells, JEV infection triggered cytochrome c release from mitochondria, which in turn activated caspase-9 and -3. Treatment of JEV-infected N18 cells with cyclosporin A or ruthenium red, which attenuate mitochondrial injuries, blocked activation of caspase-9 or -3, typifying that, in neuronal cells, this apoptosis involves the mitochondrial pathway. Alternatively, in caspase-3-cleficient MCF-7 cells, JEV persisted and readily triggered a typical apoptotic response, including cytochrome c release and full activation of caspase-9 and -8 along with caspase-6, indicating that JEV did not require caspase-3 to manifest caspase-8 activation and apoptosis. Interestingly, a Fas-associated cleathdomain-containing protein (FADD) dominant-negative mutant, which interfered with transmission of the extracellular death signals into cells through the Fas/tumour necrosis factor (TNF) receptor, failed to block JEV-induced apoptosis and caspase-8 activation, implying that receptor oligonnerization of the Fas/TNF pathway might not participate in JEV-induced apoptosis. Taken together, these results illustrate that JEV infection triggers caspase cascades involving the initiators caspase-8 and -9, probably through FAD D- independent but mitochondrion-dependent pathways.
ISSN: 0022-1317
DOI: 10.1099/vir.0.2008/000182-0
Appears in Collections:生命科學系所

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