PLoS Pathogens · 2013 · 90 citations · 137 references
Life SciencesImmunologyMolecular BiologyInflammationInnate ImmunityTranscriptional RegulationAntiviral ImmunityInflammatory SignalingInnate Immune ResponseInnate Immune Signaling PathwaysInterferon ResponsesRig-i-like ReceptorsAntiviral Innate Immune SignalingAntiviral Innate SignalingInnate Immune FunctionInnate Immune Signaling GenesInnate Immune Transcriptional RegulationInnate Immunity PathwaysRig-i-like Receptor SignalingType I Interferon Pathways
RIG-I-Like Receptors (RLRs) sense cytosolic viral RNA to transiently activate type I IFN production. Here, we report that a type I IFN inducible DExD/H helicase, DDX24, exerts a negative-regulatory effect on RLR function. Expression of DDX24 specifically suppressed RLR activity, while DDX24 loss, which caused embryonic lethality, augmented cytosolic RNA-mediated innate signaling and facilitated RNA virus replication. DDX24 preferentially bound to RNA rather than DNA species and influenced signaling by associating with adaptor proteins FADD and RIP1. These events preferentially impeded IRF7 activity, an essential transcription factor for type I IFN production. Our data provide a new function for DDX24 and help explain innate immune gene regulation, mechanisms that may additionally provide insight into the causes of inflammatory disease.
137
A Toll-like receptor recognizes bacterial DNA
Hiroaki Hemmi, Osamu Takeuchi, Taro Kawai et al. · Nature · 2000 · 6.4K citations
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Lena Alexopoulou, Agnieszka Czopik Holt, Ruslan Medzhitov et al. · Nature · 2001 · 6.1K citations
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Hiroki Kato, Osamu Takeuchi, Shintaro Sato et al. · Nature · 2006 · 3.8K citations