Coxsackievirus A6 Induces Cell Cycle Arrest in G0/G1 Phase for Viral Production

Frontiers in Cellular and Infection Microbiology
Zeng-Yan WangJing-Hua Yu

Abstract

Recent epidemiological data indicate that outbreaks of hand, foot, and mouth disease (HFMD), which can be categorized according to its clinical symptoms as typical or atypical, have markedly increased worldwide. A primary causative agent for typical HFMD outbreaks, enterovirus 71 (EV71), has been shown to manipulate the cell cycle in S phase for own replication; however, it is not clear whether coxsackievirus (CVA6), the main agent for atypical HFMD, also regulates the host cell cycle. In this study, we demonstrate for the first time that CVA6 infection arrests the host cell cycle in G0/G1-phase. Furthermore, synchronization in G0/G1 phase, but not S phase or G2/M phase, promotes viral production. To investigate the mechanism of cell cycle arrest induced by CVA6 infection, we analyzed cell cycle progression after cell cycle synchronization at G0/G1 or G2/M. Our results demonstrate that CVA6 infection promotes G0/G1 phase entry from G2/M phase, and inhibits G0/G1 exit into S phase. In line with its role to arrest cells in G0/G1 phase, the expression of cyclinD1, CDK4, cyclinE1, CDK2, cyclinB1, CDK1, P53, P21, and P16 is regulated by CVA6. Finally, the non-structural proteins of CVA6, RNA-dependent RNA polymerase 3D and protease ...Continue Reading

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Citations

Sep 2, 2020·The Journal of Microbiology·Wenbo HuoShucheng Hua
Aug 28, 2020·Frontiers in Microbiology·Liping WuXiaoyue Chen
Apr 25, 2020·Frontiers in Microbiology·Anna MajerTimothy F Booth
Jul 25, 2020·Virology Journal·Yuanzhi LiuXiaoyue Chen
Mar 3, 2020·Frontiers in Microbiology·Shuxia ZhangJinghua Yu
Nov 6, 2020·The Journal of General Virology·Zhou ShenGuiqing Peng
Apr 2, 2021·Frontiers in Cellular and Infection Microbiology·Victor Emmanuel Viana GeddesRenato Santana de Aguiar
Jun 7, 2021·Research in Veterinary Science·Erzhen DuanJinrong Wang

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorting
flow cytometry
Flow
transfection

Software Mentioned

ModFit
ModFit LT

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