Poxviruses utilize multiple strategies to prevent activation of extrinsic and intrinsic apoptotic pathways for successful replication. Mitochondrial heat shock proteins (mtHsps), especially Hsp60 and its cofactor Hsp10, are engaged in apoptosis regulation; however, until now, the influence of poxviruses on mtHsps has never been studied. We used highly infectious Moscow strain of ectromelia virus (ECTV) to investigate the mitochondrial heat shock response and apoptotic potential in permissive L929 fibroblasts. Our results show that ECTV-infected cells exhibit mostly mitochondrial localization of Hsp60 and Hsp10, and show overexpression of both proteins during later stages of infection. ECTV infection has only moderate effect on the electron transport chain subunit expression. Moreover, increase of mtHsp amounts is accompanied by lack of apoptosis, and confirmed by reduced level of pro-apoptotic Bax protein and elevated levels of anti-apoptotic Bcl-2 and Bcl-xL proteins. Taken together, we show a positive relationship between increased levels of Hsp60 and Hsp10 and decreased apoptotic potential of L929 fibroblasts, and further hypothesize that Hsp60 and/or its cofactor play important roles in maintaining protein homeostasis in mitochondria for promotion of cell survival allowing efficient replication of ECTV.

中文翻译：

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轮虫病毒诱导的线粒体热休克反应伴随着鼠L929成纤维细胞凋亡潜能的降低。

痘病毒利用多种策略来阻止外源性和内在性凋亡途径的激活，从而成功复制。线粒体热休克蛋白（mtHsps），尤其是Hsp60及其辅因子Hsp10，参与细胞凋亡的调控。但是，迄今为止，尚未研究过痘病毒对mtHsps的影响。我们使用高度传染性的莫斯科菌落病毒（ECTV）株调查了允许的L929成纤维细胞中的线粒体热休克反应和凋亡潜能。我们的结果表明，经ECTV感染的细胞主要表现出Hsp60和Hsp10的线粒体定位，并且在感染后期均显示两种蛋白的过表达。ECTV感染仅对电子传输链亚基表达有中等影响。而且，mtHsp量的增加伴随着细胞凋亡的缺乏，并由促凋亡的Bax蛋白水平降低和抗凋亡的Bcl-2和Bcl-xL蛋白水平升高证实。综上所述，我们显示出Hsp60和Hsp10的水平升高与L929成纤维细胞的凋亡潜能下降之间存在正相关，并进一步假设Hsp60和/或其辅因子在维持线粒体蛋白质稳态以促进细胞存活从而有效复制中起着重要作用ECTV。