title: MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71).
abstract: The role of the MEK1-ERK signaling cascade in the replication cycle of Enterovirus 71 (EV71), the primary cause of hand, foot and mouth disease (HFMD), has been analyzed. In vitro infection with EV71 induced a biphasic activation of ERK. The two phases of activation appeared to be triggered by different mechanisms, with the first phase being activated by the binding of viral particles to the membrane receptor of host cells and the second probably being in response to the production of new virus particles. Inhibition of ERK activation by U0126 was found to severely impair virus production. A similar reduction in EV71 replication was also observed when MEK1 expression was subject to knockdown using specific siRNAs. By contrast knockdown of MEK2 expression showed that it was dispensable for virus replication cycle, despite both MEK isoforms being activated and translocated to the nucleus equally well in response to virus infection. Overall, this study suggests distinct functions of the two isoforms of MEK in EV71 replication cycle, with an essential role for MEK1 in stimulating the ERK signaling cascade to promote virus replication. Taken together with our previous work on herpes simplex virus type 2 (HSV2) this study highlights MEK1 as a potential broad antiviral molecular target.
authors.affiliation: Department of Microbiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
authors.forename: Yihong
authors.initials: Y
authors.lastname: Peng
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D029821:Enterovirus A, Human / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D021381:Protein Transport; D034741:RNA, Small Interfering; D014162:Transfection; D014466:Ultraviolet Rays; D014779:Virus Replication / Q000187:drug effects
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009570:Nitriles; D034741:RNA, Small Interfering; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1