Mitophagy Activation Targeting PINK1 Is an Effective Treatment to Inhibit Zika Virus Replication

作者：Huang, Yike; Li, Qingyuan; Kang, Lan; Li, Bin; Ye, Haiyan; Duan, Xiaoqiong; Xie, He; Jiang, Man; Li, Shilin; Zhu, Ya; Tan, Qi; Chen, Limin^*

来源：ACS Infectious Diseases, 2023, 9(7): 1424-1436.

DOI：10.1021/acsinfecdis.3c00196

• mitophagy
• PINK1
• niclosamide
• Zikavirus
• ubiquitin

Mitophagyis a selective degradation mechanism that maintains mitochondrialhomeostasis by eliminating damaged mitochondria. Many viruses manipulatemitophagy to promote their infection, but its role in Zika virus (ZIKV)is unclear. In this study, we investigated the effect of mitophagyactivation on ZIKV replication by the mitochondrial uncoupling agentniclosamide. Our results demonstrate that niclosamide-induced mitophagyinhibits ZIKV replication by eliminating fragmented mitochondria,both in vitro and in a mouse model of ZIKV-inducednecrosis. Niclosamide induces autophosphorylation of PTEN-inducedputative kinase 1 (PINK1), leading to the recruitment of PRKN/Parkinto the outer mitochondrial membrane and subsequent phosphorylationof ubiquitin. Knockdown of PINK1 promotes ZIKV infection and rescuesthe anti-ZIKV effect of mitophagy activation, confirming the roleof ubiquitin-dependent mitophagy in limiting ZIKV replication. Thesefindings demonstrate the role of mitophagy in the host response inlimiting ZIKV replication and identify PINK1 as a potential therapeutictarget in ZIKV infection.

• 单位
  中国医学科学院北京协和医院; 哈尔滨医科大学