Human enterovirus 68 interferes with the host cell cycle to facilitate viral production

Zeng Yan Wang, Ting Zhong, Yue Wang, Feng Mei Song, Xiao Feng Yu, Li Ping Xing, Wen Yan Zhang, Jing Hua Yu, Shu Cheng Hua, Xiao Fang Yu

Research output: Contribution to journalArticle

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 the Picornaviridae family, 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.

Original languageEnglish (US)
Article number29
JournalFrontiers in cellular and infection microbiology
Volume7
Issue numberFEB
DOIs
StatePublished - Feb 8 2017
Externally publishedYes

Keywords

  • Cell cycle
  • Enterovirus 68 (EV-D68)
  • G0/G1 arrest
  • Host-pathogen interaction
  • Viral replication

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Medicine(all)
  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Wang, Z. Y., Zhong, T., Wang, Y., Song, F. M., Yu, X. F., Xing, L. P., Zhang, W. Y., Yu, J. H., Hua, S. C., & Yu, X. F. (2017). Human enterovirus 68 interferes with the host cell cycle to facilitate viral production. Frontiers in cellular and infection microbiology, 7(FEB), [29]. https://doi.org/10.3389/fcimb.2017.00029