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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


  • Wang P
  • Arjona A
  • Zhang Y
  • Sultana H
  • Dai J
  • Yang L
  • LeBlanc PM
  • Doiron K
  • Saleh M
  • Fikrig E


Nature immunology

Publication Data

October 21, 2010

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:

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