Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, Jiangsu Province, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China; Jiangsu Key Laboratory for Food Quality and Safety - State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, China.
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, Jiangsu Province, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, China; Jiangsu Key Laboratory for Food Quality and Safety - State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing, China.
Vet Microbiol. 2020 Aug;247:108787. doi: 10.1016/j.vetmic.2020.108787. Epub 2020 Jul 15.
Porcine circovirus type 2 (PCV2) is an important pathogen of the current pig industry. The Wnt signalling pathway plays an important role in the growth of young animals. In this study, we mainly elucidated the relationship between PCV2 and the Wnt signalling pathway. In an in vivo experiment in mice, we demonstrated the downregulatory effects of PCV2 infection on expression levels of downstream components of the Wnt signalling pathway. Weight loss in mice was reversed by activating the Wnt signalling pathway, and the body weight was still significantly higher than that in mice infected with PCV2. We detected levels of growth hormone (GH) in the liver and sera, which showed that GH was also downregulated in mice challenged with PCV2. Lithium chloride, the activator of Wnt signalling, upregulated GH, albeit to a significantly lesser degree than that in corresponding non-stimulated mock mice. In vitro studies showed that PCV2 infection downregulated protein expression of β-catenin and mRNA expression of matrix metallopeptidase-2 (Mmp2), downregulated protein expression of β-catenin in the cytoplasm and nucleus, and reduced the activity of the TCF/LEF promoter, demonstrating that PCV2 inhibited activation of the Wnt signalling pathway in vitro. Finally, we found that Rep protein of PCV2 might be responsible for the inhibitory effect.
猪圆环病毒 2 型（PCV2）是当前猪产业的重要病原体。Wnt 信号通路在幼小动物的生长中起着重要作用。在本研究中，我们主要阐明了 PCV2 与 Wnt 信号通路之间的关系。在小鼠体内实验中，我们证明了 PCV2 感染对 Wnt 信号通路下游成分表达水平的下调作用。激活 Wnt 信号通路可逆转小鼠体重减轻，且体重仍明显高于 PCV2 感染的小鼠。我们检测了肝脏和血清中的生长激素（GH）水平，结果表明 GH 在感染 PCV2 的小鼠中也被下调。Wnt 信号通路的激活剂氯化锂虽然能上调 GH，但上调程度明显低于相应的未刺激对照 mock 小鼠。体外研究表明，PCV2 感染下调了β-连环蛋白的蛋白表达和基质金属蛋白酶-2（Mmp2）的 mRNA 表达，下调了细胞质和细胞核中β-连环蛋白的蛋白表达，并降低了 TCF/LEF 启动子的活性，表明 PCV2 抑制了体外 Wnt 信号通路的激活。最后，我们发现 PCV2 的 Rep 蛋白可能是导致这种抑制作用的原因。
