PT  - JOURNAL ARTICLE
AU  - Lili Tao
AU  - Alexandria Lowe
AU  - Guoxun Wang
AU  - Igor Dozmorov
AU  - Tyron Chang
AU  - Nan Yan
AU  - Tiffany A. Reese
TI  - Metabolic Control of Viral Infection through PPAR-α Regulation of STING Signaling
AID  - 10.1101/731208
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 731208
4099  - http://biorxiv.org/content/early/2019/08/09/731208.short
4100  - http://biorxiv.org/content/early/2019/08/09/731208.full
AB  - Cellular metabolic pathways contribute to many aspects of viral infection and may have pro-viral as well as antiviral functions. However, specific mechanisms for metabolic regulation of antiviral immunity are not well understood. Peroxisomes are essential sites of fatty acid metabolism and regulate immune signaling. We investigated the function of peroxisomal metabolism in herpesvirus infection and innate immunity in vivo and ex vivo. We found that induction of peroxisomal activity through the activation of the nuclear receptor PPAR-α enhanced herpesvirus replication. PPAR-α activation increased reactive oxygen species (ROS), which inhibited activation of stimulator of interferon (STING), a signaling molecule in the cytosolic DNA sensing pathway that induces antiviral type I interferon. Importantly, stimulation of peroxisomal activity in mice enhanced herpesvirus replication and pathogenesis comparable to levels observed previously in type I interferon receptor knockout mice. These findings are the first to indicate that peroxisomal lipid metabolism and ROS directly regulate immunity to cytoplasmic DNA.