GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses
Journal
Nature Immunology
Journal Volume
15
Journal Issue
1
Pages
63-71
Date Issued
2014
Author(s)
Chiang, H.-S.
Zhao, Y.
Song, J.-H.
Liu, S.
Wang, N.
Terhorst, C.
Sharpe, A.H.
Basavappa, M.
Jeffrey, K.L.
Reinecker, H.-C.
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.
Type
journal article