Li, Jian and Ma, Chunmei and Long, Fei and Yang, Dongxue and Liu, Xue and Hu, Yingchao and Wu, Chunyan and Wang, Bingwei and Wang, Min and Chen, Yunzi and Liu, Genyan and Moynagh, Paul N. and Zhou, Jiawei and Peng, Tao and Yang, Shuo (2019) Parkin Impairs Antiviral Immunity by Suppressing the Mitochondrial Reactive Oxygen Species-Nlrp3 Axis and Antiviral Inflammation. iScience, 16. pp. 468-484. ISSN 2589-0042

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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.

Item Type:	Article
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords:	Parkin; Impairs; Antiviral Immunity; Mitochondrial; Reactive Oxygen; Species-Nlrp3 Axis; Antiviral Inflammation;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	13452
Identification Number:	https://doi.org/10.1016/j.isci.2019.06.008
Depositing User:	Professor Paul Moynagh
Date Deposited:	23 Oct 2020 15:28
Journal or Publication Title:	iScience
Publisher:	Cell Press
Refereed:	Yes
URI:	https://www.cell.com/iscience/home
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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