title: Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I.
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.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.forename: Alvaro
authors.initials: A
authors.lastname: Arjona
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hameeda
authors.initials: H
authors.lastname: Sultana
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.forename: Philippe M
authors.initials: PM
authors.lastname: LeBlanc
authors.forename: Karine
authors.initials: K
authors.lastname: Doiron
authors.forename: Maya
authors.initials: M
authors.lastname: Saleh
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D014901:West Nile Fever / Q000235:genetics / Q000276:immunology*; D014902:West Nile virus
chemical_list: D004268:DNA-Binding Proteins; D007370:Interferon Type I; D011991:Receptors, Virus; D014157:Transcription Factors; C490034:Trim25 protein, mouse; D044767:Ubiquitin-Protein Ligases; C506440:Casp12 protein, mouse; D053454:Caspase 12; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
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