Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response

Khantisitthiporn, Onruedee, Shue, Byron, Eyre, Nicholas S., Nash, Colt W., Turnbull, Lynne, Whitchurch, Cynthia B. ORCID: https://orcid.org/0000-0003-2296-3791, van der Hoek, Kylie H., Helbig, Karla J. and Beard, Michael R. (2021) Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response. Life Science Alliance, 4 (7). ISSN 2575-1077

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Abstract

Peroxisomes are recognized as significant platforms for the activation of antiviral innate immunity where stimulation of the key adapter molecule mitochondrial antiviral signaling protein (MAVS) within the RIG-I like receptor (RLR) pathway culminates in the up-regulation of hundreds of ISGs, some of which drive augmentation of multiple innate sensing pathways. However, whether ISGs can augment peroxisome-driven RLR signaling is currently unknown. Using a proteomics-based screening approach, we identified Pex19 as a binding partner of the ISG viperin. Viperin colocalized with numerous peroxisomal proteins and its interaction with Pex19 was in close association with lipid droplets, another emerging innate signaling platform. Augmentation of the RLR pathway by viperin was lost when Pex19 expression was reduced. Expression of organelle-specific MAVS demonstrated that viperin requires both mitochondria and peroxisome MAVS for optimal induction of IFN-β. These results suggest that viperin is required to enhance the antiviral cellular response with a possible role to position the peroxisome at the mitochondrial/ MAM MAVS signaling synapse, furthering our understanding of the importance of multiple organelles driving the innate immune response against viral infection.

Item Type: Article
Additional Information: Funding Information: This work was supported by the National Health and Medical Research Council (NHMRC) of Australia (ID#1053206, ID#1027641, ID#626906, ID#11456613).
Uncontrolled Keywords: ecology,biochemistry, genetics and molecular biology (miscellaneous),plant science,health, toxicology and mutagenesis ,/dk/atira/pure/subjectarea/asjc/2300/2303
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 04 Nov 2022 11:30
Last Modified: 01 Aug 2023 10:32
URI: https://ueaeprints.uea.ac.uk/id/eprint/89615
DOI: 10.26508/lsa.202000915

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