Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D

Jinghua Yu, Liying Zhang, Peiyou Ren, Ting Zhong, Zhaolong Li, Zengyan Wang, Jingliang Li, Xin Liu, Ke Zhao, Wenyan Zhang, Xiao Fang Yu

Research output: Contribution to journalArticle

Abstract

Many viruses disrupt the host cell cycle to facilitate their own growth. We assessed the mechanism and function of enterovirus 71 (EV71), a primary causative agent for recent hand, foot, and mouth disease outbreaks, in manipulating cell cycle progression. Our results suggest that EV71 infection induces S-phase arrest in diverse cell types by preventing the cell cycle transition from the S phase into the G2/M phase. Similar results were observed for an alternate picornavirus, Coxsackievirus A16. Synchronization in S phase, but not G0/G1 phase or G2/M phase, promotes viral replication. Consistent with its ability to arrest cells in S phase, the expression of cyclin A2, CDK 2, cyclin E1, and cyclin B1 was regulated by EV71 through increasing transcription of cyclin E1, promoting proteasome-mediated degradation of cyclin A2 and regulating the phosphorylation of CDK 2. Finally, a non-structural protein of EV71, the RNA-dependent RNA polymerase 3D, was demonstrated to mediate S-phase cell cycle arrest. These findings suggest that EV71 induces S-phase cell cycle arrest in infected cells via non-structural protein 3D, which may provide favorable conditions for virus production.

Original languageEnglish (US)
Pages (from-to)425-436
Number of pages12
JournalCell Cycle
Volume14
Issue number3
DOIs
StatePublished - Feb 1 2015

    Fingerprint

Keywords

  • Cell cycle arrest
  • Enterovirus 71 (EV71)
  • Polymerase 3D
  • Viral replication

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Yu, J., Zhang, L., Ren, P., Zhong, T., Li, Z., Wang, Z., Li, J., Liu, X., Zhao, K., Zhang, W., & Yu, X. F. (2015). Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D. Cell Cycle, 14(3), 425-436. https://doi.org/10.4161/15384101.2014.980631