Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways.
Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways.
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传染性胃肠炎病毒感染通过 FasL 和线粒体介导的途径诱导细胞凋亡
DOI：
10.1016/j.vetmic.2012.01.017
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发表时间：
2012-07-06
影响因子：
3.3
通讯作者：
Tong D
中科院分区：
文献类型：
--
作者：
Ding L;Xu X;Huang Y;Li Z;Zhang K;Chen G;Yu G;Wang Z;Li W;Tong D
据报道，传染性胃肠炎病毒（TGEV）可诱导猪睾丸（ST）细胞凋亡。然而，tgev诱导细胞凋亡的机制尚不清楚。在本研究中，我们观察到TGEV感染诱导猪肾（PK-15）细胞凋亡呈时间和剂量依赖性。TGEV感染使FasL上调，激活FasL介导的凋亡通路，导致caspase-8的激活和Bid的裂解。此外，TGEV感染下调Bcl-2，上调Bax表达，促进Bax向线粒体易位，激活线粒体介导的凋亡通路，进而引起细胞色素c的释放和caspase-9的激活。外源性和内源性途径均激活下游效应物caspase-3，随后PARP发生裂解，导致细胞凋亡。此外，在氯化铵（NH4Cl）预处理的PK-15细胞或紫外线灭活的TGEV感染的细胞中，TGEV感染没有引起明显的DNA断裂。反过来，阻断半胱天冬酶的激活也不影响TGEV的复制。综上所述，本研究表明tgev诱导的凋亡依赖于PK-15细胞中的病毒复制，并通过激活FasL和线粒体介导的凋亡途径发生。
Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH4Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.
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影响因子：
3.3
作者：
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通讯作者：
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影响因子：
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