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Home/Research/Paper Chase/GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.
GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.
Nat. Immunol..11 24, 2013;15(1):63-71.
Chiang HS, Zhao Y, Song JH, Liu S, Wang N, Terhorst C, Sharpe AH, Basavappa M, Jeffrey KL, Reinecker HC.
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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-β 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.