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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.

SUBMITTER: Wang P 

PROVIDER: S-EPMC3712356 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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

Wang Penghua P   Arjona Alvaro A   Zhang Yue Y   Sultana Hameeda H   Dai Jianfeng J   Yang Long L   LeBlanc Philippe M PM   Doiron Karine K   Saleh Maya M   Fikrig Erol E  

Nature immunology 20100905 10


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 vi  ...[more]

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