COX5B regulates MAVS-mediated antiviral signaling through interaction with ATG5 and repressing ROS production

• Published in: PLoS pathogens Vol. 8; no. 12; p. e1003086
• Main Authors: Zhao, Yuanyuan, Sun, Xiaofeng, Nie, Xuanli, Sun, Liwei, Tang, Tie-Shan, Chen, Dahua, Sun, Qinmiao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2012; Public Library of Science (PLoS)
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antiviral agents; Apoptosis; Autophagy; Autophagy-Related Protein 5; Biology; Blotting, Western; Cell Proliferation; Cells, Cultured; Control; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Health aspects; Host-parasite relationships; Humans; Immunity, Innate; Immunoprecipitation; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Mitochondria; Mitochondria - metabolism; NF-kappa B - genetics; NF-kappa B - metabolism; Pathogenesis; Pattern recognition; Physiological aspects; Protein Binding; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Signal Transduction; Studies; Vesicular Stomatitis - genetics; Vesicular Stomatitis - immunology; Vesicular Stomatitis - virology; Vesicular stomatitis Indiana virus - genetics; Viral infections; Virion - metabolism; China
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003086

Innate antiviral immunity is the first line of the host defense system that rapidly detects invading viruses. Mitochondria function as platforms for innate antiviral signal transduction in mammals through the adaptor protein, MAVS. Excessive activation of MAVS-mediated antiviral signaling leads to dysfunction of mitochondria and cell apoptosis that likely causes the pathogenesis of autoimmunity. However, the mechanism of how MAVS is regulated at mitochondria remains unknown. Here we show that the Cytochrome c Oxidase (CcO) complex subunit COX5B physically interacts with MAVS and negatively regulates the MAVS-mediated antiviral pathway. Mechanistically, we find that while activation of MAVS leads to increased ROS production and COX5B expression, COX5B down-regulated MAVS signaling by repressing ROS production. Importantly, our study reveals that COX5B coordinates with the autophagy pathway to control MAVS aggregation, thereby balancing the antiviral signaling activity. Thus, our study provides novel insights into the link between mitochondrial electron transport system and the autophagy pathway in regulating innate antiviral immunity.