Journal
EMBO REPORTS
Volume 10, Issue 8, Pages 916-922Publisher
WILEY
DOI: 10.1038/embor.2009.109
Keywords
NF-kappa B; cytomegalovirus; type I interferon; DNA sensor
Categories
Funding
- Swiss National Science Foundation
- European Union
- European Molecular Biology Organization
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Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappa B) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappa B activation remain elusive. Here, we report the identification of two receptor-interacting protein ( RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappa B signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappa B activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappa B and suggest a possible new immune modulation strategy of the MCMV.
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