PCV2 inhibits the Wnt signalling pathway in vivo and in vitro

Abstract 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.