Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway.

Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway.
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DOI:
10.3201/eid0812.020224
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发表时间:
2002-12
影响因子:
11.8
通讯作者:
Weiner DB
Weiner DB
中科院分区:
医学2区
文献类型:
--
作者:
Yang JS;Ramanathan MP;Muthumani K;Choo AY;Jin SH;Yu QC;Hwang DS;Choo DK;Lee MD;Dang K;Tang W;Kim JJ;Weiner DB

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西尼罗河病毒 (WNV) 是媒介传播病原体黄病毒科的成员。西尼罗河病毒感染的临床症状包括神经系统症状、四肢无力和脑炎,可能导致瘫痪或死亡。我们报告说,WNV 衣壳 (Cp) 本身会在组织培养物中诱导快速核浓缩和细胞死亡。细胞凋亡是通过线粒体途径诱导的,导致 caspase-9 激活和下游 caspase-3 激活。衣壳基因传递到小鼠大脑或骨骼肌的纹状体导致细胞死亡和炎症,可能是通过衣壳诱导体内细胞凋亡。这些研究表明,西尼罗河病毒的衣壳蛋白可能通过诱导细胞凋亡级联反应来负责病毒发病机制的各个方面。
West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.