STAT3在新型肠道病毒71型(EV71)感染和复制中的作用初步研究  

Effects of STAT3on enterovirus 71(EV71)infection and replication

作　　者：王艳[1] 卞良[1] 刘晴晴[1] 熊鹰[1] 李泽阳[1] 龙健儿[1] 

机构地区：[1]复旦大学基础医学院病原生物学系,上海200032

出　　处：《复旦学报（医学版）》2015年第2期166-173,186,共9页Fudan University Journal of Medical Sciences

基　　金：国家传染病重大专项(2012ZX10004503-003);国家自然科学基金基础科学人才培养项目(J1210041);上海市自然科学基金(09411964500)~~

摘　　要：目的研究STAT3(signal transducer and activator of transcription 3)对新型肠道病毒71型(enterovirus 71,EV71)感染及复制的影响。方法观察EV71感染横纹肌肉瘤细胞后STAT3的动态表达;利用慢病毒载体下调或过表达STAT3技术,观察细胞在改变STAT3表达后,对EV71感染细胞后病毒VP1表达、形成蚀斑和病毒滴度的影响,研究STAT3对EV71感染和复制的影响。结果 EV71感染可明显下调细胞STAT3-Tyr705磷酸化(p-STAT3)水平。在STAT3表达稳定下调的细胞中,p-STAT3水平也下调,这有利于EV71病毒感染和复制。而过表达STAT3的细胞内,p-STAT3水平也上调,对EV71感染和复制的效应与上述STAT3下调的结果相反。免疫共聚焦和蚀斑分析发现高表达p-STAT3的细胞不易被EV71感染。结论EV71感染可明显下调p-STAT3水平,并促进病毒的复制。STAT3影响EV71的感染和复制,可能主要通过STAT3的磷酸化水平影响细胞对病毒的易感性。Objective To identify the roles of signal transducer and activator of transcription 3（STAT3）in enterovirus 71（EV71）infection and replication. Methods According to the observations of the kinetics of STAT3 in rhabdomysarcoma（RD）cells after EV71 infection,and the detection of the effects of loss-and gain-of-function of STAT3（by knocked-in a short-hairpin RNA or a STAT3 gene into the cellular genome with a lentivirus vector,respectively）on the expression of EV71VP1,virus plaque-forming,and virus titer after EV71 infection,we evaluated host STAT3 roles in EV71 infection and replication. Results The level of phosphorylated STAT3-Tyr^705（pY^705-STAT3）was down-regulated significantly after EV71 infection.In the RD cells knocked-down STAT3,pSTAT3 was also down-regulated.The knock-down of STAT3 promoted EV71 infection and replication.By contrast,over-expression of STAT3 showed the opposite effects on EV71 infection.Confocal microscopy analysis and plaque-forming assay indicated that high level of p-STAT3 decreased the cellular susceptibility to EV71 infection. Conclusions Our data indicated that host STAT3 has an important role in EV71 infection and replication,which may be induced by the doen-regulation of phosphorylated p-STAT3 level.Therefore,EV71 infection increased the cellular susceptibility to the virus and promoted the viral replication.

关 键 词：EV71 STAT3 横纹肌肉瘤细胞 

分 类 号：R738.7[医药卫生—肿瘤]