Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caspase 12 / genetics
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Caspase 12 / metabolism*
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Cells, Cultured
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DEAD Box Protein 58
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DEAD-box RNA Helicases / metabolism*
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DNA-Binding Proteins / metabolism
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Fibroblasts / metabolism
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Immunity, Innate
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Interferon Type I / biosynthesis*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neurons / metabolism
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Receptors, Virus / metabolism*
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Signal Transduction
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Transcription Factors / metabolism
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Ubiquitin-Protein Ligases / metabolism
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Ubiquitination
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West Nile Fever / genetics
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West Nile Fever / immunology*
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West Nile virus*
Substances
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DNA-Binding Proteins
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Interferon Type I
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Receptors, Virus
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Transcription Factors
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Trim25 protein, mouse
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Ubiquitin-Protein Ligases
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Casp12 protein, mouse
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Caspase 12
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Ddx58 protein, mouse
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DEAD Box Protein 58
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DEAD-box RNA Helicases