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Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.

Nature immunology | Oct 21, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20818395

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

Mesh terms: 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

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Associated grants

  • Agency: Canadian Institutes of Health Research, Id: 79410
  • Agency: NIAID NIH HHS, Id: AI-055749
  • Agency: NIAID NIH HHS, Id: AI-50031
  • Agency: NIAID NIH HHS, Id: N01AI50031
  • Agency: NIAID NIH HHS, Id: R01 AI055749
  • Agency: NIAID NIH HHS, Id: U54-AI057158
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

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