title: Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells.
abstract: 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.
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors: Tatsuya
authors: T
authors: Saitoh
authors: Takashi
authors: T
authors: Satoh
authors: Naoki
authors: N
authors: Yamamoto
authors: Satoshi
authors: S
authors: Uematsu
authors: Osamu
authors: O
authors: Takeuchi
authors: Taro
authors: T
authors: Kawai
authors: Shizuo
authors: S
authors: Akira
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D000090123:Viperin Protein
chemical_list: D007370:Interferon Type I; D011506:Proteins; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; C417529:Rsad2 protein, mouse; D000090123:Viperin Protein