Lv Xiaoling, Zhao Kui, Lan Yungang, Li Zi, Ding Ning, Su Jingjing, Lu Huijun, Song Deguang, Gao Feng, He Wenqi
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University Changchun, China.
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University Changchun, China.
Front Microbiol. 2017 Mar 1;8:304. doi: 10.3389/fmicb.2017.00304. eCollection 2017.
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.
猪血凝性脑脊髓炎病毒（PHEV）是一种具有高度神经毒性的冠状病毒，可导致仔猪出现神经症状，如肌肉震颤、后肢麻痹和眼球震颤。在PHEV感染引起神经损伤的过程中，一些因素是否影响病毒的复制和增殖尚未完全明确。近年来，一些报道表明，miRNA可能在病毒感染中起关键调节作用。在本研究中，我们发现miR-21a-5p在感染PHEV的小鼠大脑和N2a细胞中显著上调，并且通过双荧光素酶报告基因检测发现它通过直接靶向CASK相互作用蛋白1（Caskin1）的3'-UTR来下调Caskin1的表达。在宿主中过表达miR-21a-5p或敲低Caskin1显著促进PHEV增殖。相反，用miR-21a-5p抑制剂沉默miR-21a-5p可抑制病毒增殖。综上所述，我们的结果表明Caskin1是miR-21a-5p的直接靶基因，通过下调Caskin1有利于病毒增殖。这些发现可能有助于开发治疗应用策略。
