Coxsackievirus A16 infection induces neural cell and non-neural cell apoptosis in vitro.

Coxsackievirus A16 infection induces neural cell and non-neural cell apoptosis in vitro.
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DOI:
10.1371/journal.pone.0111174
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhang W
Zhang W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li Z;Yu J;Liu L;Wei Z;Ehrlich ES;Liu G;Li J;Liu X;Wang H;Yu XF;Zhang W

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柯萨奇病毒A16(Coxsackievirus A16,CA 16)是引起手足口病(Handfoot and mouth disease,HFMD)的主要病原体之一。病毒复制通常导致宿主细胞凋亡。尽管已有报道CA 16感染可诱导人横纹肌肉瘤(Rhabdomyosarcoma,RD)细胞凋亡,但CA 16是否能诱导多种细胞凋亡,尤其是具有重要临床意义的神经细胞凋亡尚不清楚。在目前的研究中,发现CA 16感染在体外神经细胞和非神经细胞中诱导类似的凋亡反应,包括核碎裂、DNA碎裂和磷脂酰丝氨酸易位。通常不知道CA16在体内会导致严重的神经系统症状。为了进一步明确临床症状与细胞凋亡之间的相关性,对来自不同临床特征患者的两株CA 16菌株进行了研究。结果表明,无论感染患者是否有神经系统症状,CA16菌株均可导致神经和肌肉细胞凋亡。此外,机制研究表明,CA 16感染诱导凋亡通过相同的机制在神经和非神经细胞,即通过激活线粒体(内在)途径相关的caspase 9蛋白和Fas死亡受体(外在)途径相关的caspase 8蛋白。了解CA16感染诱导神经和非神经细胞凋亡的机制将有助于更好地理解CA16的发病机制。
Coxsackievirus A16 (CA16) is one of the main causative pathogens of hand, foot and mouth disease (HFMD). Viral replication typically results in host cell apoptosis. Although CA16 infection has been reported to induce apoptosis in the human rhabdomyosarcoma (RD) cell line, it remains unclear whether CA16 induces apoptosis in diverse cell types, especially neural cells which have important clinical significance. In the current study, CA16 infection was found to induce similar apoptotic responses in both neural cells and non-neural cells in vitro, including nuclear fragmentation, DNA fragmentation and phosphatidylserine translocation. CA16 generally is not known to lead to serious neurological symptoms in vivo. In order to further clarify the correlation between clinical symptoms and cell apoptosis, two CA16 strains from patients with different clinical features were investigated. The results showed that both CA16 strains with or without neurological symptoms in infected patients led to neural and muscle cell apoptosis. Furthermore, mechanistic studies showed that CA16 infection induced apoptosis through the same mechanism in both neural and non-neural cells, namely via activation of both the mitochondrial (intrinsic) pathway-related caspase 9 protein and the Fas death receptor (extrinsic) pathway-related caspase 8 protein. Understanding the mechanisms by which CA16 infection induces apoptosis in both neural and non-neural cells will facilitate a better understanding of CA16 pathogenesis.
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