Inhibition of apoptosis prevents West Nile virus induced cell death.
Inhibition of apoptosis prevents West Nile virus induced cell death.
复制标题
抑制细胞凋亡可防止西尼罗河病毒诱导的细胞死亡。
DOI：
10.1186/1471-2180-7-49
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发表时间：
2007-05-29
期刊：
影响因子：
4.2
通讯作者：
Cinatl, Jindrich, Jr.
中科院分区：
文献类型：
--
作者：
Kleinschmidt, Malte C.;Michaelis, Martin;Ogbomo, Henry;Doerr, Hans-Wilhelm;Cinatl, Jindrich, Jr.
西尼罗河病毒（WNV）感染可导致人类严重的脑膜炎和脑炎。细胞凋亡最近被证明有助于西尼罗河病毒脑炎的发病机制。在这里，我们使用WNV感染的胶质瘤细胞来研究WNV复制和WNV诱导的人脑源性细胞凋亡。T98 G细胞高度允许裂解性WNV感染，如感染性病毒滴度的产生和特征性细胞病变效应的发展所证明的。WNV复制降低细胞活力并诱导细胞凋亡，如通过激活效应物半胱天冬酶-3、引发剂半胱天冬酶-8和-9、聚（ADP-核糖）聚合酶（PARP）裂解和从线粒体释放细胞色素c所示。BID的截断表明外在和内在凋亡途径之间的串扰。半胱天冬酶-8或-9的抑制可抑制PARP裂解，表明两种半胱天冬酶均参与WNV诱导的细胞凋亡。泛半胱天冬酶抑制剂防止WNV诱导的细胞凋亡，而不影响病毒复制。我们发现，西尼罗河病毒感染诱导细胞死亡的脑源性肿瘤细胞系T98 G的细胞凋亡参与的成分的外在以及内在的凋亡途径。我们的研究结果阐明了WNV诱导神经细胞死亡的分子机制。
West Nile virus (WNV) infection can cause severe meningitis and encephalitis in humans. Apoptosis was recently shown to contribute to the pathogenesis of WNV encephalitis. Here, we used WNV-infected glioma cells to study WNV-replication and WNV-induced apoptosis in human brain-derived cells. T98G cells are highly permissive for lytic WNV-infection as demonstrated by the production of infectious virus titre and the development of a characteristic cytopathic effect. WNV replication decreased cell viability and induced apoptosis as indicated by the activation of the effector caspase-3, the initiator caspases-8 and -9, poly(ADP-ribose)polymerase (PARP) cleavage and the release of cytochrome c from the mitochondria. Truncation of BID indicated cross-talk between the extrinsic and intrinsic apoptotic pathways. Inhibition of the caspases-8 or -9 inhibited PARP cleavage, demonstrating that both caspases are involved in WNV-induced apoptosis. Pan-caspase inhibition prevented WNV-induced apoptosis without affecting virus replication. We found that WNV infection induces cell death in the brain-derived tumour cell line T98G by apoptosis under involvement of constituents of the extrinsic as well as the intrinsic apoptotic pathways. Our results illuminate the molecular mechanism of WNV-induced neural cell death.
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