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Published on: January 12, 2015
Both ERK1 and ERK2 are required for enterovirus 71 (EV71) efficient replication
Meng Zhu1, Hao Duan2, Meng Gao3
1Department of Microbiology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. mengzhu1984@gmail.com.
Abstract:
It has been demonstrated that MEK1, one of the two MEK isoforms in Raf-MEK-ERK1/2 pathway, is essential for successful EV71 propagation. However, the distinct function of ERK1 and ERK2 isoforms, the downstream kinases of MEKs, remains unclear in EV71 replication. In this study, specific ERK siRNAs and selective inhibitor U0126 were applied. Silencing specific ERK did not significantly impact on the EV71-caused biphasic activation of the other ERK isoform, suggesting the EV71-induced activations of ERK1 and ERK2 were non-discriminative and independent to one another. Knockdown of either ERK1 or ERK2 markedly impaired progeny EV71 propagation (both by more than 90%), progeny viral RNA amplification (either by about 30% to 40%) and protein synthesis (both by around 70%), indicating both ERK1 and ERK2 were critical and not interchangeable to EV71 propagation. Moreover, suppression of EV71 replication by inhibiting both early and late phases of ERK1/2 activation showed no significant difference from that of only blocking the late phase, supporting the late phase activation was more importantly responsible for EV71 life cycle. Taken together, this study for the first time identified both ERK1 and ERK2 were required for EV71 efficient replication and further verified the important role of MEK1-ERK1/2 in EV71 replication.
Insights
Both ERK1 and ERK2 are crucial for enterovirus 71 (EV71) replication, with the late phase of their activation being particularly important for the virus life cycle.
Area of Science:
- Virology
- Molecular Biology
- Cell Signaling
Background:
- The Raf-MEK-ERK1/2 pathway is vital for viral propagation.
- MEK1 is essential for EV71 replication, but the roles of ERK1 and ERK2 remain unclear.
Purpose of the Study:
- To investigate the distinct functions of ERK1 and ERK2 in EV71 replication.
- To determine the importance of ERK1/2 activation phases in the EV71 life cycle.
Main Methods:
- Used specific ERK small interfering RNAs (siRNAs) for gene silencing.
- Applied the selective MEK inhibitor U0126.
- Assessed EV71 propagation, RNA amplification, and protein synthesis.
Main Results:
- Silencing ERK1 or ERK2 significantly impaired EV71 propagation, RNA amplification, and protein synthesis.
- ERK1 and ERK2 activations were independent and non-discriminative during EV71 infection.
- Inhibiting the late phase of ERK1/2 activation was sufficient to suppress EV71 replication.
Conclusions:
- Both ERK1 and ERK2 are essential and non-interchangeable for efficient EV71 replication.
- The late phase of ERK1/2 activation plays a critical role in the EV71 life cycle.
- Confirms the significance of the MEK1-ERK1/2 pathway in EV71 replication.
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