RT Journal Article
SR Electronic
T1 Viperin interacts with PEX19 to mediate peroxisomal augmentation of the innate antiviral response
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000915
DO 10.26508/lsa.202000915
VO 4
IS 7
A1 Onruedee Khantisitthiporn
A1 Byron Shue
A1 Nicholas S Eyre
A1 Colt W Nash
A1 Lynne Turnbull
A1 Cynthia B Whitchurch
A1 Kylie H Van der Hoek
A1 Karla J Helbig
A1 Michael R Beard
YR 2021
UL https://www.life-science-alliance.org/content/4/7/e202000915.abstract
AB 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.