细胞MEK1/2蛋白及其相关通路在单纯疱疹病毒Ⅱ型(HSV-2)复制中的作用  

Key Role of MEK1/2-ERK Pathway in Replication of Type Ⅱ Herpes Simplex Virus (HSV-2)

作　　者：屠静[1] 张浩[1] 周琦[1] 王波[1] 曹眸[1] 黄海[2] 彭宜红[1] 

机构地区：[1]北京大学医学部病原微生物学系,北京100083 [2]北京航空航天大学宇航学院,北京100083

出　　处：《中国生物化学与分子生物学报》2008年第9期839-845,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.30470084和10472007);国家高技术发展研究项目(863计划,No.2007AA02Z317)资助~~

摘　　要：基于细胞Raf/MEK/ERK信号通路与病毒复制的关系,应用Western印迹检测p-ERK1/2蛋白的表达、用终点滴定法测定病毒增殖量(TCID50),以及观察感染细胞的细胞病变效应(CPE)等,揭示单纯疱疹病毒Ⅱ型(HSV-2)复制与ERK通路的关系.结果表明,HSV-2的复制可引起细胞ERK通路的活化;用U0126预先抑制ERK通路的活化,或用特异性siRNA敲减MEK1/2基因的表达可显著地抑制病毒复制.提示ERK信号通路以及MEK1/2蛋白对HSV-2的复制具有重要的作用.该研究对进一步阐明细胞ERK通路各激酶蛋白在病毒复制中的作用机制、寻找抗病毒作用靶标等奠定了良好的基础.Herpes simplex virus type 2（HSV-2） is an important pathogen that causes sexually transmitted genital infections worldwide.Now no specific therapeutic drugs or preventive vaccines are available.Recently,it has been reported that Raf/MEK/ERK（ERK） signal pathway is relevant with virus amplification.MEK1/2 are the key components of the ERK pathway.Thus,we investigated whether MEK1/2 and its associated ERK pathway were required for virus replication.By Western blot analysis,end-point assay for virus titer,and microscopic observation of cytopathic effect（CPE） of viral infection,we demonstrated that ERK pathway was activated within the cells where HSV-2 replicated.Moreover,the inhibition of the ERK signaling pathway by MEK1/2 inhibitor U0126 significantly impaired HSV-2 progeny production,which correlated with the suppression of p-ERK1/2 expression in infected cells.Furthermore,the knockdown of MEK1/2 by specific small interfering RNA（siRNAs） also obviously blocked HSV-2 replication.The results indicated that MEK1/2 and its associated ERK pathway play an essential role in the replication of HSV-2.Silencing the expression of MEK1/2 and perturbing the ERK signaling pathway exhibit an evident anti-HSV-2 effect,suggesting that it can serve as a potential target for a therapeutic drug.

关 键 词：单纯疱疹病毒Ⅱ型 ERK信号通路 MEK1/2 小干扰RNA 

分 类 号：Q936[生物学—微生物学]