糖原合酶激酶-3介导β-catenin抑制猪流行性腹泻病毒的增殖  

GLYCOGEN SYNTHASE KINASE-3(GSK-3)-MEDIATED β-CATENIN INHIBITING THE PROLIFERATION OF PORCINE EPIDEMIC DIARRHOEA VIRUS

作　　者：左叶雯 孔宁[1] 李智丽[2] 童武[1] 焦亚娟 王桦 郑浩[1] 高飞[1] 孙大格 于海[1] 李丽薇[1] 虞凌雪[1] 童光志[1] 单同领[1] ZUO Ye-wen;KONG Ning;LI Zhi-li;TONG Wu;JIAO Ya-juan;WANG Hua;ZHENG Hao;GAO Fei;SUN Da-ge;YU Hai;LI Li-wei;YU Ling-xue;TONG Guang-zhi;SHAN Tong-ling(Shanghai Veterinary Research Institute,CAAS,Shanghai 200241,China;Henan University of Science and Technology,Luoyang 471023,China)

机构地区：[1]中国农业科学院上海兽医研究所,上海200241 [2]河南科技大学,洛阳471023

出　　处：《中国动物传染病学报》2018年第5期16-22,共7页Chinese Journal of Animal Infectious Diseases

基　　金：国家重点研发计划项目(2016YFD0500103);国家自然科学基金(31502071)

摘　　要：糖原合成酶激酶-3(glycogen synthase kinase-3,GSK-3)是一种丝氨酸/苏氨酸蛋白激酶,能够促进细胞内多种蛋白质的磷酸化,从而参与调控细胞的多种抗病毒功能。其中β-catenin是GSK-3信号通路下游的一个重要转录调节因子,能够被GSK-3磷酸化,磷酸化的β-catenin能够被细胞内泛素化蛋白酶体降解途径降解。为探究GSK-3/β-catenin在猪流行性腹泻病毒(Porcine epidemic diarrhoea virus,PEDV)复制过程中所发挥的作用,本研究通过在Marc-145细胞上分别抑制GSK-3的活性和Wnt/β-catenin通路后感染PEDV,检测结果显示,抑制GSK-3的活性后,β-catenin含量增加,并且能够抑制PEDV的增殖;抑制Wnt/β-catenin通路后,β-catenin含量降低,促进PEDV在Marc-145细胞上的增殖。结果表明,PEDV感染Marc-145细胞后,宿主细胞能够下调GSK-3的活性,并进一步上调β-catenin的含量,从而抑制病毒在细胞内的增殖。本研究从分子层面上解释了GSK-3介导β-catenin在病毒复制过程中的作用,为PED的防控与治疗提供了一定的指导意义。Glycogen synthase kinase-3(GSK-3)is a serine/threonine protein kinase,which can promote the phosphorylation of many proteins to play a strong biological role in regulating various antiviral activities in cells.β-catenin is an important transcriptional regulator that can be phosphorylated by GSK-3 and eventually degraded by proteasome pathway.In order to investigate whether GSK-3/β-catenin passway played an important role in the replication of Porcine epidemic diarrhea virus(PEDV),we infected Marc-145 cells with PEDV after respective inhibition of the activities of GSK-3 and Wnt/β-catenin pathways.The results showed that when the content ofβ-catenin increased and the proliferation of PEDV was inhibited due to inhibition of the activity of GSK-3,and further inhibition of Wnt/β-catenin pathway.On the contrary,the proliferation of PEDV on Marc-145 cells increased when the content ofβ-catenin decreased.These results suggested that the decrease of GSK-3 activity would lead the expression ofβ-catenin increase that inhibited the proliferation of PEDV in Marc-145 cells.This study explained the role ofβ-catenin mediated by GSK-3 in the process of virus replication,providing some guidance for the study of the pathogenesis,prevention and control of PED.

关 键 词：糖原合成酶激酶-3 Β-CATENIN 猪流行性腹泻病毒 

分 类 号：S852.659.6[农业科学—基础兽医学]