Ubiquitin in the activation and attenuation of innate antiviral immunity

Heaton, Steven M.; Borg, Natalie A.; Dixit, Vishva M.

The retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular PRRs. The RLRs sense invasive RNA produced during infection by both RNA and DNA viruses (Schlee, 2013) . RLR engagement up-regulates type-I IFN (IFN-I) expression, which in turn stimulates transcription of hundreds of IFN-stimulated genes (ISGs) that commit host and nearby cells to an antiviral posture. Recognized for their role in antibacterial immunity, the NLRs are emerging as antiviral mediators that regulate both IFN-I and NF-κB activation. These are also activated by TLRs, a cell-specific class of extracellular and endosomal transmembrane PRRs that sense a broad spectrum of pathogenic motifs. RLR, NLR, and TLR signaling proteins must be spatially and temporally coordinated for efficient immune signal transduction.