BACKGROUND Bovine parainfluenza virus type 3 (BPIV3) is one of the important viral respiratory agents associated with the bovine respiratory disease complex (BRDC) in cattle. Previous study has demonstrated that infection of BPIV3 causes innate immune response within the host cell. β-catenin is a key component of the Wnt/β-catenin signal pathway which is involved in the regulation of interferon-beta (IFN-β) transcription. Some viruses can activate while others can inhibit the Wnt/β-catenin signaling pathway. However, the role of β-catenin in BPIV3 infection remains unclear. RESULTS Here we found that the expression of β-catenin mRNA was up-regulated and β-catenin protein was down-regulated after BPIV3 infection in MDBK cells. Moreover, it was confirmed that overexpression of β-catenin suppressed BPIV3 replication and knockdown of β-catenin promoted viral replication, suggesting that β-catenin inhibits BPIV3 replication. Furthermore, IFN-β signal pathway and virus titer analysis using the GSK3β inhibitor (LiCl) revealed that Wnt/β-catenin can serve as a mechanism to suppress virus replication in infected cells. The results indicated that LiCl promoted the expression and accumulation in the nucleus of β-catenin, which further promoted the expression of IFN-β and OSA1 and suppressed BPIV3 replication. Most importantly, BPIV3 down-regulating β-catenin protein expression was due to degradation of GSK3β mediated proteasome pathway. CONCLUSIONS In summary, we discovered the relationship between β-catenin and BPIV3 replication. These results provided further insight into the study of BPIV3 pathogenesis.

中文翻译：

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β-连环蛋白通过先天免疫途径抑制牛副流感病毒3型复制。

背景技术3型牛副流感病毒（BPIV3）是与牛中的牛呼吸道疾病复合物（BRDC）有关的重要病毒呼吸道药物之一。先前的研究表明，感染BPIV3会在宿主细胞内引起先天性免疫反应。β-catenin是Wnt /β-catenin信号通路的关键组成部分，参与了干扰素-β（IFN-β）转录的调控。一些病毒可以激活，而另一些可以抑制Wnt /β-catenin信号传导途径。然而，β-连环蛋白在BPIV3感染中的作用尚不清楚。结果在BPDB3感染MDBK细胞后，我们发现β-cateninmRNA的表达上调，而β-catenin蛋白的表达下调。此外，证实了β-连环蛋白的过表达抑制了BPIV3的复制，而敲低β-连环蛋白促进了病毒的复制，表明β-连环蛋白抑制了BPIV3的复制。此外，使用GSK3β抑制剂（LiCl）进行的IFN-β信号通路和病毒滴度分析表明，Wnt /β-catenin可以作为抑制病毒在感染细胞中复制的机制。结果表明，LiCl促进了β-catenin在细胞核中的表达和积累，进而促进了IFN-β和OSA1的表达，并抑制了BPIV3的复制。最重要的是，BPIV3下调β-catenin蛋白的表达是由于GSK3β介导的蛋白酶体途径的降解。结论总之，我们发现了β-catenin与BPIV3复制之间的关系。