2. Academic Validation
  3. Mitophagy Activation Targeting PINK1 Is an Effective Treatment to Inhibit Zika Virus Replication

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

  • ACS Infect Dis. 2023 Jun 10. doi: 10.1021/acsinfecdis.3c00196.
Yike Huang 1,  Qingyuan Li 2,  Lan Kang 1,  Bin Li 3,  Haiyan Ye 1,  Xiaoqiong Duan 1,  He Xie 4,  Man Jiang 5,  Shilin Li 1,  Ya Zhu 1,  Qi Tan 1,  Limin Chen 1 3 4
Affiliations

Affiliations

  • 1 Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory for Transfusion-transmitted Infectious Diseases of the Health Commission of Sichuan Province, Chengdu 610052, Sichuan, China.
  • 2 North Sichuan Medical College, Nanchong 637000, Sichuan, China.
  • 3 Joint Laboratory on Transfusion-transmitted Infectious Diseases between Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Nanning Blood Center, Nanning Blood Center, Key Laboratory for Transfusion-transmitted Infectious Diseases of the Health Commission of Nanning City, Nanning 530007, Guangxi, China.
  • 4 The Hospital of Xidian Group, Xian 710077, Shaanxi, China.
  • 5 Department of Pharmacology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150000, Heilongjiang, China.
PMID: 37300493 DOI: 10.1021/acsinfecdis.3c00196
Abstract

Mitophagy is a selective degradation mechanism that maintains mitochondrial homeostasis by eliminating damaged mitochondria. Many viruses manipulate Mitophagy to promote their Infection, but its role in Zika virus (ZIKV) is unclear. In this study, we investigated the effect of Mitophagy activation on ZIKV replication by the mitochondrial uncoupling agent niclosamide. Our results demonstrate that niclosamide-induced Mitophagy inhibits ZIKV replication by eliminating fragmented mitochondria, both in vitro and in a mouse model of ZIKV-induced necrosis. Niclosamide induces autophosphorylation of PTEN-induced putative kinase 1 (PINK1), leading to the recruitment of PRKN/Parkin to the outer mitochondrial membrane and subsequent phosphorylation of ubiquitin. Knockdown of PINK1 promotes ZIKV Infection and rescues the anti-ZIKV effect of Mitophagy activation, confirming the role of ubiquitin-dependent Mitophagy in limiting ZIKV replication. These findings demonstrate the role of Mitophagy in the host response in limiting ZIKV replication and identify PINK1 as a potential therapeutic target in ZIKV Infection.

Keywords

PINK1; Zika virus; mitophagy; niclosamide; ubiquitin.

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