GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.
Nat Immunol
; 15(1): 63-71, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24270516
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-ß 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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
RNA Viral
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Transdução de Sinais
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Fatores de Troca de Nucleotídeo Guanina Rho
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Imunidade Inata
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Microtúbulos
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article