Mitophagy in TGEV infection counteracts oxidative stress and apoptosis.

Mitophagy in TGEV infection counteracts oxidative stress and apoptosis.
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TGEV 感染中的线粒体自噬抵消氧化应激和细胞凋亡

DOI:
10.18632/oncotarget.8345
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发表时间:
2016-05-10
期刊:
影响因子:
--
通讯作者:
Yang Q
Yang Q
中科院分区:
其他
文献类型:
--
作者:
Zhu L;Mou C;Yang X;Lin J;Yang Q

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肠上皮细胞含有大量线粒体,具有持久吸收和屏障功能。线粒体的选择性自噬(mitophagy)在线粒体的质量控制和细胞稳态的维持中发挥着重要作用。传染性胃肠炎病毒(TGEV)是一种猪肠道致病性冠状病毒,可引起哺乳仔猪吸收不良和致命的水样腹泻。线粒体自噬在TGEV感染引起的病理变化中的作用尚不清楚。在这里,我们报道TGEV诱导线粒体自噬来抑制猪上皮细胞(IPEC-J2)中病毒感染诱导的氧化应激和细胞凋亡。我们观察到TGEV感染引起线粒体损伤、形态异常、线粒体自噬完全、TGEV感染后无明显细胞凋亡。同时,TGEV还诱导DJ-1和一些抗氧化基因上调,以抑制病毒感染引起的氧化应激。此外,沉默 DJ-1 可抑制 TGEV 感染后的线粒体自噬并增加细胞凋亡。此外,我们首次证明病毒核衣壳蛋白(N)在病毒感染过程中位于线粒体和线粒体吞噬体中或单独表达。这些结果为进一步改进TGEV感染的预防和治疗提供了新的视角。这些结果表明TGEV感染诱导线粒体自噬以促进细胞存活并可能促进病毒感染。
The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.
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