In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 126.4-126.4
Abstract:
The cytosolic innate-immune receptor RIG-I is very important for the detection and host response against several RNA-viruses. During viral challenge, RIG-I activates mitochondria-associated adaptor MAVS to recruit several downstream cytosolic signaling proteins, resulting in transcription factor IRF3 activation and Type-I interferons transcription (TI-IFN). However, the mechanisms coupling activation of organelle-anchored MAVS with key downstream cytosolic components is incompletely understood. Through a human genome-wide RNAI screen, we identified several novel regulators of RIG-I signaling. Furthermore, we identified a key novel scaffolding protein (named RIG-I assembly mediator protein, RAMP) that links MAVS with downstream TBK1 activation, IRF3 phosphorylation and TI-IFN transcription during virus infection. RAMP functioned as a scaffolding platform that interacted and assembled a complex containing MAVS, TBK1, NEMO and IRF3. Lack of RAMP expression led to the failure of MAVS to interact with downstream NEMO, TBK1, and IRF3. Recombinant RAMP supported IRF3 activation in a cell free assay. RAMP was essential for antiviral cellular resistance, and infection induced subcellular re-localization of RAMP. Furthermore, our data demonstrated that RAMP and TRAF proteins act in parallel to transduce signals from MAVS to IRF3. This study provided important novel insights into the regulation and assembly of the RIG-I signalosome and TI-IFN response.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.126.4
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5
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