Department of Microbiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China.
Antiviral Res. 2012 Jan;93(1):110-7. doi: 10.1016/j.antiviral.2011.11.001. Epub 2011 Nov 13.
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.
MEK1-ERK 信号级联在肠道病毒 71 型（EV71）复制周期中的作用，EV71 是手足口病（HFMD）的主要病原体，已被分析。EV71 的体外感染诱导 ERK 的双相激活。这两个激活阶段似乎是由不同的机制触发的，第一阶段是由病毒颗粒与宿主细胞的膜受体结合激活的，第二阶段可能是对新病毒颗粒的产生的反应。发现 U0126 抑制 ERK 激活会严重损害病毒的产生。当使用特异性 siRNA 使 MEK1 表达失活时，也观察到 EV71 复制的类似减少。相比之下，MEK2 表达的敲低表明它对于病毒复制周期是可有可无的，尽管两种 MEK 同工型在响应病毒感染时都被同等程度地激活并易位到核内。总的来说，这项研究表明 MEK 的两种同工型在 EV71 复制周期中具有不同的功能，MEK1 在刺激 ERK 信号级联以促进病毒复制方面具有重要作用。结合我们之前关于单纯疱疹病毒 2 型（HSV2）的工作，这项研究强调 MEK1 是一个潜在的广谱抗病毒分子靶点。
