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

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Nature Immunology (Impact Factor: 20). 10/2010; 11(10):912-9. DOI: 10.1038/ni.1933
Source: PubMed


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.

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Available from: Penghua Wang, Dec 17, 2013
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    • "Recent study has indicated the role of caspase-12 in controlling WNV infection via RIG-I. Caspase-12 has been shown to regulate E3-ligase TRIM-25 mediated ubiquitination of RIG-I, an essential signaling event required for the type I interferon response (Wang et al., 2010). Also most recently it has been shown that RIG-I plays an important role in mounting type I interferon response in human brain microvascular endothelial cells following DENV infection (da Conceicao et al., 2013). "
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    • "Caspases are a family of aspartic acid–specific cysteine-dependent proteases mainly involved in apoptotic and inflammatory signaling pathways. During WNV infection, Caspase 12 has been found to be required for an effective antiviral innate response by regulating the ubiquitination of RIG-I through the tripartite motif (TRIM) 25 mediated pathway (Wang et al., 2010). "

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