Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Diagnosis, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, China; School of Pharmacy, Linyi University, Linyi, 276000, China.
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Diagnosis, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing 210014, China.
Vet Microbiol. 2020 Feb;241:108573. doi: 10.1016/j.vetmic.2019.108573. Epub 2019 Dec 31.
Caprine parainfluenza virus type 3 (CPIV3) is the one of most common causative agents of caprine respiratory infection, resulting in significant economic losses in the goat and sheep industries. However, the molecular mechanisms and host genes involved in the pathogenesis of and immunity against CPIV3 infection remain poorly understood. In this study, we used RNA-Seq to understand the responses of madin-darby bovine kidney (MDBK) cells to CPIV3 infection. A total of 261 differentially-expressed genes (DEGs) were identified in CPIV3-infected compared with mock-infected MDBK cells at 24 h post-infection (hpi). The DEGs were mainly involved in immune system processes, metabolic processes, and signal transduction. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the most significantly enriched signaling pathways were MAPK, Wnt, PI3K-Akt, tumor necrosis factor, Toll-like receptor and ubiquitin-mediated proteolysis. STRING analysis revealed that seven interferon-stimulated genes (ISGs) were upregulated (IFI6, ISG15, OAS1Y, OAS1Z, MX1, MX2 and RSAD2) and may play a pivotal role during CPIV3 infection. Moreover, overexpression of these ISGs significantly reduced CPIV3 replication in vitro, while siRNA silencing markedly improved CPIV3 replication 24 and 48 hpi. Ours is the first study to profile the gene expression of CPIV3-infected MDBK cells. We identified seven ISGs that could be targeted in novel antiviral strategies against CPIV3.
羊副流感病毒 3 型（CPIV3）是引起山羊呼吸道感染的最常见病原体之一，给山羊和绵羊养殖业造成了重大经济损失。然而，CPIV3 感染的发病机制和免疫的分子机制和宿主基因仍知之甚少。在这项研究中，我们使用 RNA-Seq 来了解 MDBK 细胞对 CPIV3 感染的反应。在 CPIV3 感染的 MDBK 细胞与对照感染的 MDBK 细胞相比，在感染后 24 小时（hpi）共鉴定出 261 个差异表达基因（DEGs）。DEGs 主要参与免疫系统过程、代谢过程和信号转导。京都基因与基因组百科全书（KEGG）分析表明，最显著富集的信号通路是 MAPK、Wnt、PI3K-Akt、肿瘤坏死因子、Toll 样受体和泛素介导的蛋白质水解。STRING 分析显示，七个干扰素刺激基因（ISGs）上调（IFI6、ISG15、OAS1Y、OAS1Z、MX1、MX2 和 RSAD2），并可能在 CPIV3 感染过程中发挥关键作用。此外，这些 ISGs 的过表达显著降低了 CPIV3 在体外的复制，而 siRNA 沉默则显著提高了 CPIV3 在 24 和 48 hpi 的复制。这是首次对 CPIV3 感染的 MDBK 细胞进行基因表达谱分析的研究。我们鉴定了七个 ISGs，它们可能成为针对 CPIV3 的新型抗病毒策略的靶点。
