Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production

Frontiers in Cellular and Infection Microbiology

Wang, Yue¹  Song, Feng-mei²  Xing, Li-ping³  Hua, Shu-cheng³  Wang, Zeng-yan³  Zhang, Wen-yan⁴  Yu, Xiao-feng⁴  Yu, Jing-hua⁴  Yu, Xiao-fang⁴  Zhong, Ting⁵ 

[1] Chemistry of Traditional Chinese Medicine, College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China;Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin Univrsity, Changchun, China;Department of Internal Medicine, The First Hospital of Jilin University, Jilin University, Changchun, China;Institute of Virology and AIDS Research, The First Hospital of Jilin University, Jilin University, Changchun, China;Medicinal Chemistry, College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China

关键词: Enterovirus 68 (EV-D68);    Cell Cycle;    G0/G1 arrest;    viral replication;    host-pathogen interaction;   

DOI  :  10.3389/fcimb.2017.00029

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY