Antiviral Protein Viperin Promotes Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Type I Interferon Production in Plasmacytoid Dendritic Cells

Toll-like receptor 7 (TLR7) and TLR9 sense viral nucleic acids and induce production of type I interferon (IFN) by plasmacytoid dendritic cells (pDCs) to protect the host from virus infection. We showed that the IFN-inducible antiviral protein Viperin promoted TLR7- and TLR9-mediated production of type I IFN by pDCs. Viperin expression was potently induced after TLR7 or TLR9 stimulation and Viperin localized to the cytoplasmic lipid-enriched compartments, lipid bodies, in pDCs. Viperin interacted with the signal mediators IRAK1 and TRAF6 to recruit them to the lipid bodies and facilitated K63-linked ubiquitination of IRAK1 to induce the nuclear translocation of transcription factor IRF7. Loss of Viperin reduced TLR7- and TLR9-mediated production of type I IFN by pDCs. However, Viperin was dispensable for the production of type I IFN induced by intracellular nucleic acids. Thus, Viperin mediates its antiviral function via the regulation of the TLR7 and TLR9-IRAK1 signaling axis in pDCs.