No abstract

The RIG-I-like receptors, retinoic acid inducible gene-1 (RIG-I), melanoma differentiation-associated protein 5, and laboratory of genetics and physiology-2, are cytoplasmic sensors for RNA viruses that mediate the antiviral innate immune responses. We demonstrate that really interesting new gene-finger domain-and K homology domain-containing MEX3C regulates RIG-I function. MEX3C colocalizes with RIG-I in the stress granules of virally infected cells, and its overexpression causes the lysine-63-linked ubiquitination of RIG-I and activates IFN-β promoter. Embryonic fibroblast cells, macrophages, and conventional dendritic cells derived from Mex3c-deficient mice showed defective production of type I IFN after infection with RNA viruses that are recognized by RIG-I. These results demonstrate that MEX3C is an E3 ubiquitin ligase that modifies RIG-I in stress granules and plays a critical role in eliciting antiviral immune responses.signal transduction | cytoplasmic puncta

Nucleotide-binding domain and leucine rich repeat containing gene family receptors (NLRs) are cytosolic proteins that respond to a variety of pathogen and host components to induce inflammatory cytokines. NLRC5 is a recently identified member of the NLR family that has been implicated in positive and negative regulation of antiviral innate immune responses. To clarify whether NLRC5 controls antiviral innate immunity in vivo, we generated NLRC5-deficient mice. Macrophages and dendritic cells derived from NLRC5-deficient mice induced relatively normal levels of IFN-β, IL-6, and TNF-α after treatment with RNA viruses, DNA viruses, and bacteria. The serum cytokine levels after polyinosinic-polycytidylic acid infection were also comparable between control and NLRC5-deficient mice. NLRC5 overexpression promoted IL-1β production via caspase-1, suggesting that NLRC5 constitutes an inflammasome. However, there was no reduction of IL-1β in NLRC5-deficient cells in response to known inflammasome activators, suggesting that NLRC5 controls IL-1β production through an unidentified pathway. These findings indicate that NLRC5 is dispensable for cytokine induction in virus and bacterial infections under physiologic conditions.