Ruminant Disease Research Center, College of Life Science, Shandong Normal University, Shandong Province, China.
Vet Microbiol. 2021 Aug;259:109127. doi: 10.1016/j.vetmic.2021.109127. Epub 2021 May 26.
MicroRNAs (miRNAs), as a kind of small noncoding RNAs, have been proved to play a regulatory role in virus infection. However, the role and mechanism of cellular miRNAs in bovine transient fever virus (BEFV) infection are largely unknown. In the present study, we found that bta-miR-101 was significantly up-regulated in the Madin-Darby Bovine Kidney (MDBK) cells upon BEFV infection. Notably, bta-miR-101 mimic dramatically inhibited BEFV replication, while bta-miR-101 inhibitor facilitated BEFV replication, suggesting that bta-miR-101 acted as an anti-viral host factor restraining BEFV replication. Subsequently, NF-κB repressing factor (NKRF) was identified as a target gene of bta-miR-101 by dual luciferase reporter assay, and bta-miR-101 mimic significantly down-regulated expression of NKRF, while bta-miR-101 inhibitor up-regulated its expression, respectively. Furthermore, NKRF could induce apoptosis, and favored the replication of BEFV. Finally, bta-miR-101 inhibited BEFV-induced apoptosis via targeting NKRF to suppress virus replication. In general, our study provides a novel mechanism for bta-miR-101 to exert its antiviral function, which provides a theoretical basis for the development of antiviral strategy.
微小 RNA（miRNAs）作为一种小型非编码 RNA，已被证明在病毒感染中发挥调节作用。然而，细胞 miRNA 在牛暂时发热病毒（BEFV）感染中的作用和机制在很大程度上尚不清楚。在本研究中，我们发现 BEFV 感染 Madin-Darby 牛肾（MDBK）细胞后，bta-miR-101 显著上调。值得注意的是，bta-miR-101 模拟物可显著抑制 BEFV 复制，而 bta-miR-101 抑制剂则促进 BEFV 复制，表明 bta-miR-101 作为一种抗病毒宿主因子抑制 BEFV 复制。随后，双荧光素酶报告基因检测实验鉴定 NF-κB 抑制因子（NKRF）为 bta-miR-101 的靶基因，bta-miR-101 模拟物显著下调 NKRF 的表达，而 bta-miR-101 抑制剂则分别上调其表达。此外，NKRF 可诱导细胞凋亡，并有利于 BEFV 的复制。最后，bta-miR-101 通过靶向 NKRF 抑制病毒复制来抑制 BEFV 诱导的细胞凋亡。总的来说，我们的研究为 bta-miR-101 发挥其抗病毒功能提供了一种新的机制，为抗病毒策略的发展提供了理论依据。
