Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
Caspase-12 has been shown to negatively modulate inflammasome signaling during bacterial infection. Its function in viral immunity, however, has not been characterized. We now report an important role for caspase-12 in controlling viral infection via the pattern-recognition receptor RIG-I. After challenge with West Nile virus (WNV), caspase-12-deficient mice had greater mortality, higher viral burden and defective type I interferon response compared with those of challenged wild-type mice. In vitro studies of primary neurons and mouse embryonic fibroblasts showed that caspase-12 positively modulated the production of type I interferon by regulating E3 ubiquitin ligase TRIM25-mediated ubiquitination of RIG-I, a critical signaling event for the type I interferon response to WNV and other important viral pathogens.
Pubmed ID: 20818395 RIS Download
Animals | Caspase 12 | Cells, Cultured | DEAD-box RNA Helicases | DNA-Binding Proteins | Fibroblasts | Immunity, Innate | Interferon Type I | Mice | Mice, Inbred C57BL | Mice, Knockout | Neurons | Receptors, Virus | Signal Transduction | Transcription Factors | Ubiquitin-Protein Ligases | Ubiquitination | West Nile Fever | West Nile virus