Viperin links lipid bodies to immune defense

Abstract

Viperin is an interferon-stimulated gene that exerts antiviral effects. In this issue of Immunity, Saitoh et al. (2011) uncovered an unexpected function of Viperin and lipid bodies in interferon induction by Toll-like receptors, specifically in plasmacytoid dendritic cells.

Figure 1. Type-I interferon induction by endosomal TLRs in plasmacytoid dendritic cells

Detection of DNA and RNA in the lumen of endosomes by TLR9 and TLR7, respectively, triggers signal transduction cascades leading to the production of type-I interferons (IFN) and inflammatory cytokines. Distinct endosomes are formed during the process of endosome maturation, which accompanies the process of TLR activation (e.g., TLR9 is activated by proteolytic processing in acidified endosomes), and the recruitment of signaling proteins including MyD88, IRAK4, IRAK1, TRAF6 and TRAF3. Recruitment of these proteins to distinct endosomes leads to the activation of NF-κB and IRF7, which in turn govern the production of inflammatory cytokines and IFN, respectively. Secreted IFN binds to IFN receptor and activates the JAK-STAT pathway to induce many IFN-stimulated genes (ISGs). One of these ISGs is Viperin, which is localized on the cytosolic surface of lipid bodies. Viperin assembles a signaling complex on lipid bodies, greatly facilitating IRF7 activation, thereby contributing to high levels of IFNα production in pDCs.