Interferon-stimulated genes inhibit caprine parainfluenza virus type 3 replication in Madin-Darby bovine kidney cells
Interferon-stimulated genes inhibit caprine parainfluenza virus type 3 replication in Madin-Darby bovine kidney cells
复制标题
干扰素刺激基因抑制山羊副流感病毒 3 型在 Madin-Darby 牛肾细胞中的复制
DOI：
10.1016/j.vetmic.2019.108573
复制
发表时间：
2020-02-01
影响因子：
3.3
通讯作者：
Zhang, Wenwen
中科院分区：
文献类型：
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作者：
Li, Jizong;Mao, Li;Zhang, Wenwen
山羊副流感病毒3型(CPIV3)是引起山羊呼吸道感染最常见的病原之一，给养羊业造成了巨大的经济损失。然而，CPIV3感染的分子机制和宿主基因在CPIV3感染的发病和免疫中的作用尚不清楚。在这项研究中，我们使用RNA-Seq来了解Madin-Darby牛肾(MDBK)细胞对CPIV3感染的反应。在感染后24小时，CPIV3感染的MDBK细胞与模型感染的MDBK细胞相比，共鉴定出261个差异表达基因(DEG)。DEGS主要参与免疫系统过程、代谢过程和信号转导。京都基因和基因组百科全书(KEGG)分析表明，最显著丰富的信号通路是MAPK、Wnt、PI3K-Akt、肿瘤坏死因子、Toll样受体和泛素介导的蛋白分解。序列分析显示有7个干扰素刺激基因(ISGs)上调(IFI6、ISG15、OAS1Y、OASIZ、MX1、MX2和RSAD2)，可能在CPIV3感染过程中起关键作用。此外，这些ISGs的过表达在体外显著降低了CPIV3的复制，而siRNA沉默显著地提高了CPIV3的复制24和48HPI。我们的研究首次对CPIV3感染的MDBK细胞的基因表达进行了分析。我们确定了7个ISG，它们可以作为针对CPIV3的新型抗病毒策略的靶点。
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, OASIZ, 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.