miR-21a-5p Contributes to Porcine Hemagglutinating Encephalomyelitis Virus Proliferation via Targeting CASK-Interactive Protein1 In vivo and vitro.
miR-21a-5p Contributes to Porcine Hemagglutinating Encephalomyelitis Virus Proliferation via Targeting CASK-Interactive Protein1 In vivo and vitro.
复制标题
miR-21a-5p 通过靶向 CASK 相互作用蛋白 1 促进猪血凝脑脊髓炎病毒体内和体外增殖
DOI：
10.3389/fmicb.2017.00304
复制
发表时间：
2017
影响因子：
5.2
通讯作者：
He W
中科院分区：
文献类型：
--
作者：
Lv X;Zhao K;Lan Y;Li Z;Ding N;Su J;Lu H;Song D;Gao F;He W
猪血凝性脑脊髓炎病毒（PHEV）是一种高度神经毒性的冠状病毒，可导致仔猪出现肌肉震颤、后肢麻痹和眼球震颤等神经症状。在PHEV感染引起的神经损伤过程中，是否有影响病毒复制和增殖的因素尚未完全清楚。近年来，有研究表明，miRNA可能在病毒感染过程中发挥重要的调控作用。在本研究中，我们发现miR-21 a-5 p在PHEV感染的小鼠和N2 a细胞中表达显著上调，并通过双荧光素酶报告基因检测下调CASK相互作用蛋白1（Caskin 1）的表达。宿主中miR-21 a-5 p或Caskin 1敲低的过表达显著促进PHEV增殖。相反，通过miR-21 a-5 p抑制剂沉默miR-21 a-5 p抑制了病毒增殖。综上所述，我们的研究结果表明，Caskin 1是miR-21 a-5 p的直接靶基因，下调Caskin 1的表达有利于病毒的增殖。这些发现可能有助于开发治疗应用的策略。
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that can cause nervous symptoms in piglets with muscle tremors, hind limb paralysis, and nystagmus. Whether some factors affect virus replication and proliferation had not been fully understood in the course of nerve damage caused by PHEV infection. In recent years, some reports suggested that miRNA might play a key regulatory role in viral infection. In this study, we found the miR-21a-5p is notably up-regulated in the brains of mice and N2a cells infected with PHEV, and it down-regulated the expression of CASK-interactive protein1 (Caskin1) by directly targeting the 3′-UTR of Caskin1 using a Dual-Luciferase reporter assay. The over-expression of miR-21a-5p or Caskin1 knockdown in the host significantly contributes to PHEV proliferation. Conversely, the silencing of miR-21a-5p by miR-21a-5p inhibitors suppressed the virus proliferation. Taken together, our results indicate that Caskin1 is the direct target gene of miR-21a-5p, and it is advantageous to virus proliferation by down-regulating Caskin1. These findings may help in the development of strategies for therapeutic applications.