Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu Province, China.
Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, Nanjing, Jiangsu Province, China.
BMC Genomics. 2020 Feb 4;21(1):123. doi: 10.1186/s12864-020-6539-7.
Duck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings remains poorly understood. To study the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 by high-throughput sequencing.
We found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed genes (DEGs) in livers of mock-infected and DHAV-3-infected duckling. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways, including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway, were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Furthermore, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during DHAV-3 infection. And some host miRNAs were predicted to target the DHAV-3 genome.
This is the first integrated analysis of miRNA and mRNA in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. These findings increase our knowledge of the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis. They also aid in the understanding of host-virus interactions.
鸭甲型肝炎病毒 3 型(DHAV-3)是养鸭业中最具危害性的病原体之一。然而,DHAV-3 感染雏鸭的分子机制仍知之甚少。为了研究 miRNA-mRNA 的遗传调控网络以及 DHAV-3 感染雏鸭涉及的信号通路,我们通过高通量测序对致死性 DHAV-3 感染的雏鸭肝脏进行了全局 miRNA 和 mRNA 表达谱分析。
我们在模拟感染和 DHAV-3 感染的雏鸭肝脏中发现了 156 个差异表达 miRNA(DEM)和 7717 个差异表达基因(DEG)。在基于这些 DEM 和 DEG 构建的 miRNA-mRNA 网络中,共鉴定出 19606 对具有负相关表达模式的 miRNA-mRNA 对。此外,通过分析网络中对 DHAV-3 感染有反应的 mRNAs 的功能,发现免疫相关通路,包括细胞因子-细胞因子受体相互作用、细胞凋亡、Toll 样受体、Jak-STAT 和 RIG-I 样受体信号通路,显著富集。此外,apl-miR-32-5p、apl-miR-125-5p、apl-miR-128-3p、apl-miR-460-5p 和 novel-m0012-3p 被鉴定为 DHAV-3 感染期间免疫相关信号通路中的潜在调节因子。并且一些宿主 miRNA 被预测靶向 DHAV-3 基因组。
这是首次对 DHAV-3 感染雏鸭的 miRNA 和 mRNA 进行综合分析。结果表明,miRNA 在调节免疫反应基因方面发挥着重要作用,并揭示了 DHAV-3 感染雏鸭肝脏中与免疫相关的 miRNA-mRNA 调控网络。这些发现增加了我们对 miRNA 及其靶基因在 DHAV-3 复制和发病机制中的作用的认识。它们还有助于理解宿主-病毒相互作用。