Porcine parvovirus infection induces necroptosis of porcine placental trophoblast cells via a ZBP1-mediated pathway.

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Ning Xu, Qian Du, Yijiao Cheng, Lichen Nie, Peipei Ma, Dingwen Feng, Yong Huang, Dewen Tong
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引用次数: 0

Abstract

Porcine parvovirus (PPV) infection induces germ cell death, leading to reproductive disorders in first-pregnant sows. Porcine placental trophoblast cells (PTCs) are the major target of PPV, and we have previously found that PPV infection leads to the death of PTCs by a non-apoptotic process, which may be related to PPV pathogenicity. The Z-nucleic acid-binding protein 1 (ZBP1) is often activated after virus invasion and mediates subsequent cell death. Here, we found that PPV infection induced ZBP1-mediated necroptosis of porcine PTCs in the presence of the apoptosis inhibitor, AC-DEVD-CHO. ZBP1 expression was upregulated during PPV infection, and ZBP1 knockout or RNA interference significantly reduced its expression along with the PPV-induced necroptosis. We discovered that RIPK3 and MLKL, but not Caspase-8, were involved in downstream signaling of ZBP1 during PPV infection; the phosphorylation levels of RIPK3 and MLKL were enhanced, but Caspase-8 was not significantly cleaved. The knockout of RIPK3 and MLKL significantly reduced the PPV infection-induced necroptosis of porcine PTCs. RIPK3 knockout did not affect the PPV infection-induced upregulation of ZBP1 expression, but blocked the activation of MLKL. MLKL knockout did not affect the upregulation of ZBP1 expression and RIPK3 phosphorylation during PPV infection. UV-inactivated PPV induced significantly less necroptosis of porcine PTCs than non-irradiated PPV. A PPV strain with a mutation in the translation initiation codon was still able to induce necroptosis of PTCs through the ZBP1/RIPK3/MLKL pathway. These results provide new insights into the pathogenic mechanism of PPV infection and suggest that PPV infection of porcine PTCs induces necroptosis through the viral DNA-dependent ZBP1/RIPK3/MLKL pathway.

猪细小病毒感染通过zbp1介导的途径诱导猪胎盘滋养细胞坏死。
猪细小病毒(PPV)感染诱导生殖细胞死亡,导致首次怀孕母猪的生殖障碍。猪胎盘滋养细胞(ptc)是PPV的主要靶点,我们之前发现PPV感染导致ptc通过非凋亡过程死亡,这可能与PPV的致病性有关。z -核酸结合蛋白1 (ZBP1)通常在病毒入侵后被激活并介导随后的细胞死亡。本研究发现,在细胞凋亡抑制剂AC-DEVD-CHO存在的情况下,PPV感染诱导zbp1介导的猪ptc坏死。ZBP1的表达在PPV感染期间上调,敲除ZBP1或RNA干扰ZBP1的表达随PPV诱导的坏死性坏死而显著降低。我们发现在PPV感染期间,RIPK3和MLKL参与ZBP1的下游信号传导,而Caspase-8不参与;RIPK3和MLKL的磷酸化水平升高,但Caspase-8没有明显断裂。敲除RIPK3和MLKL可显著降低PPV感染诱导的猪ptc坏死。RIPK3敲除不影响PPV感染诱导的ZBP1表达上调,但阻断了MLKL的激活。在PPV感染期间,敲除MLKL不影响ZBP1表达和RIPK3磷酸化的上调。与未照射的PPV相比,紫外线灭活PPV诱导的猪ptc坏死明显减少。翻译起始密码子突变的PPV菌株仍然能够通过ZBP1/RIPK3/MLKL途径诱导ptc坏死。这些结果为PPV感染的致病机制提供了新的见解,并提示PPV感染猪ptc通过病毒dna依赖的ZBP1/RIPK3/MLKL途径诱导坏死性坏死。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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