Yang Yifei, Tian Jijing, Zhang Haijing, Ma Meng, Li Han, Liu Tianlong, Yang Yue, Liu Ting, She Ruiping
Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing, 100700, China; Lab of Animal Pathology and Public Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Lab of Animal Pathology and Public Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
Virus Res. 2021 Sep;302:198369. doi: 10.1016/j.virusres.2021.198369. Epub 2021 Mar 5.
Recently, hepatitis E virus (HEV) has caused large outbreaks and presented a significant public health problem. Thus, the mechanism of HEV has attracted increasing research attention. Previous studies revealed that HEV infection induced hepatocyte injuries and structural and functional changes in mitochondria. These pathological changes affected the life cycle of hepatocytes. However, the precise underlying mechanism and the effector protein responsible for this process remain unclear. In the present study, mitochondrial function and the expression of mitophagy-associated mRNA transcripts and proteins were detected in an HEV- infected Mongolian gerbil model. Observation of ultrastructural changes in the liver of the inoculated group revealed the disappearance of mitochondrial cristae of mitochondrion, blurring of the bilayer structure and cavitation in the cytoplasm. The results showed that the mitochondrial transmembrane potential of decreased, mitochondrial transition pore (MPTP) opening increased, reactive oxygen species (ROS) production increased, and glutathione peroxidase (GSH-Px) activity decreased in the HEV-inoculated group. Moreover, the LC3, Beclin1, BNIP3L, Parkin, PINK1 and P62 mRNA levels were significantly increased (p < 0.05 and p < 0.01) in the inoculated group. Western blot and immunohistochemistry assay analyses detected the upregulation of the mitophagy-associated proteins LC3, Beclin1, BNIP3L, Parkin, PINK1 and P62 (p < 0.05 and p < 0.01) in HEV-infected gerbils. All these data demonstrated that HEV infection in vivo induced mitochondrial dysfunction and the activation of the mitophagy pathway, which might be one of the key factors in hepatocyte injury.
最近，戊型肝炎病毒（HEV）引发了大规模疫情，成为一个重大的公共卫生问题。因此，HEV的发病机制已引起越来越多的研究关注。以往研究表明，HEV感染会导致肝细胞损伤以及线粒体结构和功能的改变。这些病理变化影响了肝细胞的生命周期。然而，这一过程的确切潜在机制以及负责该过程的效应蛋白仍不清楚。在本研究中，我们在HEV感染的蒙古沙鼠模型中检测了线粒体功能以及与线粒体自噬相关的mRNA转录本和蛋白质的表达。对接种组肝脏超微结构变化的观察显示，线粒体嵴消失，双层结构模糊，细胞质中出现空泡。结果表明，接种HEV组的线粒体跨膜电位降低，线粒体通透性转换孔（MPTP）开放增加，活性氧（ROS）生成增加，谷胱甘肽过氧化物酶（GSH-Px）活性降低。此外，接种组中LC3、Beclin1、BNIP3L、Parkin、PINK1和P62的mRNA水平显著升高（p<0.05和p<0.01）。蛋白质印迹法和免疫组织化学分析检测到HEV感染的沙鼠中线粒体自噬相关蛋白LC3、Beclin1、BNIP3L、Parkin、PINK1和P62上调（p<0.05和p<0.01）。所有这些数据表明，体内HEV感染会诱导线粒体功能障碍和线粒体自噬途径的激活，这可能是肝细胞损伤的关键因素之一。
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