Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-Nlrp3 Axis and Antiviral Inflammation

Jian Li, Chunmei Ma, Fei Long, Dongxue Yang, Xue Liu, Yingchao Hu, Chunyan Wu, Bingwei Wang, Min Wang, Yunzi Chen, Genyan Liu, Paul N. Moynagh, Jiawei Zhou, Tao Peng*, Shuo Yang

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)
39 Downloads (Pure)

Abstract

Although mitochondria are known to be involved in host defense against viral infection, the physiological role of mitophagy, a crucial mechanism for maintaining mitochondrial homeostasis, in antiviral immunity remains poorly defined. Here, we show that Parkin, a central player in mitophagy, has a vital function in regulating host antiviral responses. Parkin-knockout mice exhibit improved viral clearance and survival after viral infection. However, Parkin deficiency does not affect antiviral signaling and interferon production. Instead, Parkin deficiency augments innate antiviral inflammation by enhancing mitochondrial ROS (mtROS)-mediated NLRP3 inflammasome activation and promoting viral clearance. Loss of NLRP3 can reverse the enhanced antiviral responses in Parkin knockout mice. Furthermore, we find that Parkin expression is downregulated in peripheral blood mononuclear cells of patients infected with virus. Collectively, our results suggest that Parkin plays an important role in antiviral immunity by controlling mtROS-NLRP3 axis-mediated inflammation. These findings provide physiological insight of the importance of mitophagy in regulating host antiviral response.

Original languageEnglish
Pages (from-to)468-484
Number of pages17
JournaliScience
Volume16
DOIs
Publication statusPublished - 28 Jun 2019

Keywords

  • Biochemistry
  • Biological Sciences
  • Cell Biology
  • Genetics
  • Immunology
  • Molecular Biology

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-Nlrp3 Axis and Antiviral Inflammation'. Together they form a unique fingerprint.

Cite this