EV71 virus reduces Nrf2 activation to promote production of reactive oxygen species in infected cells

Gut Pathogens

Research

Zhenzi Bai¹  Xiaonan Zhao¹  Chenghua Li¹  Hongyan Li¹  Chuanlun Sheng¹ 

[1] Infectious Department, China-Japan Union Hospital, Jilin University, No.126, Xiantai Street, Economic Development Zone, 130033, Changchun, Jilin, China;

关键词: EV71 virus;    Keap1;    Nrf2;    ROS;    Apoptosis;    Inflammation;   

DOI  :  10.1186/s13099-020-00361-w

 received in 2019-07-24, accepted in 2020-04-15,  发布年份 2020

来源: Springer

【 摘 要 】

BackgroundEmerging evidence closely links Enterovirus 71 (EV71) infection with the generation of reactive oxygen species (ROS). Excess ROS results in apoptosis and exacerbates inflammatory reactions. The Keap1–Nrf2 axis serves as an essential oxidant counteracting pathway.MethodsThe present study aimed to elucidate the role of the Keap1–Nrf2 pathway in modulating apoptosis and inflammatory reactions triggered by oxidative stress in Vero and RD cells upon EV71 infection.ResultsElevated ROS production was identified in EV71 infected Vero and RD cells. The percentage of dead cells and expression of inflammation-promoting cytokines were increased in these cells. EV71 infected cells also displayed reinforced Keap1 expression and abrogated Nrf2 expression. Keap1 silencing resulted in the downstream aggregation of the Nrf2 protein and heme oxygenase-1 HO-1. Keap1 silencing repressed ubiquitination and reinforced Nrf2 nuclear trafficking. Furthermore, silencing Keap1 expression repressed ROS production, cell death, and inflammatory reactions in EV71 infected RD and Vero cells. In contrast, silencing of both Keap1 and Nrf2 restored ROS production, cell death, and inflammatory reactions. Nrf2 and Keap1 modulated the stimulation of the Akt sensor and extrinsic as well as intrinsic cell death pathways, resulting in EV71-triggered cell death and inflammatory reactions.ConclusionsEV71 infection can trigger ROS production, cell death, and inflammatory reactions by modulating the Nrf2 and Keap1 levels of infected cells.

【 授权许可】

CC BY   
© The Author(s) 2020

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