title: Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production.
abstract: Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of thePicornaviridaefamily, EV-A71, differs from EV-D68 in that G0/G1 synchronization inhibits, rather than promotes, EV-A71 viral replication. However, these viruses are similar in that G2/M synchronization inhibits the production and activity of both viruses, which is suggestive of a common therapeutic target for both types of enterovirus. These results further clarify the pathogenic mechanisms of enteroviruses and provide a potential strategy for the treatment and prevention of EV-D68-related disease.
authors.affiliation: Department of Internal Medicine, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Zeng-Yan
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Medicinal Chemistry, College of Pharmacy, Changchun University of Chinese Medicine Changchun, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhong
authors.affiliation: Chemistry of Traditional Chinese Medicine, College of Pharmacy, Changchun University of Chinese Medicine Changchun, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin Univrsity Changchun, China.
authors.forename: Feng-Mei
authors.initials: FM
authors.lastname: Song
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Xing
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Hua
authors.affiliation: Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University Changchun, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
mesh_terms: D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D002460:Cell Line; D002478:Cells, Cultured; D030016:Enterovirus D, Human / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D014779:Virus Replication
keywords: G0/G1 arrest; cell cycle; enterovirus 68 (EV-D68); host-pathogen interaction; viral replication