Regulation of RIG-I signaling by a a novel interferon-inducible short form of RIG-I
Final Report Abstract
Retinoic acid inducible gene I (RIG-I) is a cytoplasmic sensor of viral RNA, which triggers the innate immune response to viral infection especially the type I interferon (IFN) response. To prevent autoimmunity and immunopathology, type I IFN responses need to be tightly regulated. We identifed a novel mechanism of autoregulation of the RIG-I receptor by an IFN-inducible short isoform of RIG-I, which is generated by proteolytic cleavage. The novel short isoform is signaling inactive due to the lack of the caspase activation and recruitment domains (CARDs). It inhibits activation of RIG-I and thereby prevents type I IFN production in response to viral infection. The negative regulatory activity of the short isoform depends on the interaction of the specific binding groove within the C-terminal domain with the 5’-triphophate RNA ligand. The short isoform of RIG-I is strongly induced and sustained during acute RNA virus infection in humans in vivo, as observed in peripheral blood mononuclear cells after Yellow Fever vaccination. Thus, we have identified a novel mechanism of functional diversification of RIG-I that is involved in the control of innate antiviral immunity and may be critical to prevent immunopathology in the context of viral infection and interferonopathies.
Publications
- (2014). Nucleic acid recognition in dendritic cells. Methods Molecular Biology, 1169, 55-65
Heiseke, A., Eisenächer, K., Krug, A.
(See online at https://dx.doi.org/10.1007/978-1-4939-0882-0_6)
