Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells

Immunity. 2011 Mar 25;34(3):352-63. doi: 10.1016/j.immuni.2011.03.010.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation / immunology
  • Immunohistochemistry
  • Interferon Type I / drug effects
  • Interferon Type I / immunology*
  • Mice
  • Mice, Knockout
  • Proteins / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Toll-Like Receptor 7 / immunology*
  • Toll-Like Receptor 9 / immunology*

Substances

  • Interferon Type I
  • Proteins
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
  • vig1 protein, mouse