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

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-? 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.

SUBMITTER: Chiang HS

PROVIDER: S-EPMC4066330 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Chiang Hao-Sen HS Zhao Yun Y Song Joo-Hye JH Liu Song S Wang Ninghai N Terhorst Cox C Sharpe Arlene H AH Basavappa Megha M Jeffrey Kate L KL Reinecker Hans-Christian HC

Nature immunology 20131124 1

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 ph ...[more]

PMID: 24270516

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