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水貂肠炎病毒可通过线粒体信号通路诱导细胞凋亡

【字体:

  近日,中国农业科学院特产研究所特种动物病原与免疫创新团队首次证明水貂肠炎病毒及其非结构蛋白1通过线粒体信号通路诱导细胞凋亡,该发现为进一步解释该病毒的致病机制提供了理论基础。相关研究成果在线发表在《病毒学杂志(Journal of Virology)》上。

  水貂肠炎病毒属于细小病毒科成员,该科病毒具有感染宿主广泛,危害严重等特点,感染的水貂出现剧烈腹泻、胃肠黏膜充血、白细胞减少为主要的临床症状,给全世界水貂养殖业造成巨大的经济损失。目前已经被证实多种细小病毒及其非结构蛋白1具有诱导细胞凋亡的能力,然而关于水貂肠炎病毒及其病毒蛋白诱导细胞凋亡的分子机理仍不明确。

  该研究首先发现水貂肠炎病毒在体内、体外均诱导细胞凋亡的发生。感染病毒的水貂消化道出现不同程度的病理变化、含有大量的凋亡细胞;在体外试验发现,水貂肠炎病毒能抑制细胞增值、细胞周期停滞在G1期和诱导细胞凋亡。该团队进一步发现非结构蛋白1具有抑制细胞活性、细胞毒性和诱导细胞凋亡的能力,而其他病毒蛋白不具有这些功能。为了进一步明确该蛋白哪个结构域在诱导细胞凋亡过程中起到关键作用,研究采用截短表达和定点突变两种策略,分别对蛋白不同结构域单独表达和不同结构域的关键位点进行点突变,结果发现只有完整的非结构蛋白1具有诱导细胞凋亡的能力。分析发现,非结构蛋白1通过线粒体信号通路诱导细胞凋亡的发生,线粒体的膜电位去极化、通透性增加、线粒体内的凋亡因子被释放到细胞质中,并且导致细胞内活性氧的提高;进一步研究发现非结构蛋白1具有激活p38 MAPK和p53的作用,从而介导了线粒体信号通路引起的细胞凋亡。

  该研究得到国家自然科学基金青年科学基金、中国农科院科技创新工程、吉林省青年科研基金支持。(通讯员 王冬昭)

  原文链接:https://jvi.asm.org/content/early/2019/08/29/JVI.01249-19

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