Abstract
Detailed understanding of the signaling intermediates that confer the sensing of intracellular viral nucleic acids for induction of type I interferons is critical for strategies to curtail viral mechanisms that impede innate immune defenses. Here we show that the activation of the microtubule-associated guanine nucleotide exchange factor GEF-H1, encoded by Arhgef2, is essential for sensing of foreign RNA by RIG-I-like receptors. Activation of GEF-H1 controls RIG-I-dependent and Mda5-dependent phosphorylation of IRF3 and induction of IFN-b expression in macrophages. Generation of Arhgef2-/- mice revealed a pronounced signaling defect that prevented antiviral host responses to encephalomyocarditis virus and influenza A virus. Microtubule networks sequester GEF-H1 that upon activation is released to enable antiviral signaling by intracellular nucleic acid detection pathways.
Original language | English (US) |
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Pages (from-to) | 63-71 |
Number of pages | 9 |
Journal | Nature immunology |
Volume | 15 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology