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Nat Immunol. 2014 Jan;15(1):63-71. doi: 10.1038/ni.2766. Epub 2013 Nov 24.

GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.

Author information

1
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School.
2
Division of Immunology, Beth Israel Deaconess Medical Center and Center for the Study of Inflammatory Bowel Disease, Harvard Medical School.
3
Department of Microbiology, Harvard Medical School, Boston, Massachusetts 02114, USA.
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Contributed equally

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-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.

PMID:
24270516
PMCID:
PMC4066330
DOI:
10.1038/ni.2766
[Indexed for MEDLINE]
Free PMC Article

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