title: Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D.
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.
authors: a Institute of Virology and AIDS Research ; The First Hospital of Jilin University; Jilin University ; Changchun , Jilin , China.
authors: Jinghua
authors: J
authors: Yu
authors: Liying
authors: L
authors: Zhang
authors: Peiyou
authors: P
authors: Ren
authors: Ting
authors: T
authors: Zhong
authors: Zhaolong
authors: Z
authors: Li
authors: Zengyan
authors: Z
authors: Wang
authors: Jingliang
authors: J
authors: Li
authors: Xin
authors: X
authors: Liu
authors: Ke
authors: K
authors: Zhao
authors: Wenyan
authors: W
authors: Zhang
authors: Xiao-Fang
authors: XF
authors: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D029821:Enterovirus A, Human / Q000378:metabolism*; D004769:Enterovirus Infections / Q000378:metabolism / Q000473:pathology; D016195:G2 Phase; D006801:Humans; D008938:Mitosis; D060888:Real-Time Polymerase Chain Reaction; D016196:S Phase; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D017361:Viral Nonstructural Proteins
keywords: cell cycle arrest; enterovirus 71 (EV71); polymerase 3D; viral replication