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

Hao Sen Chiang, Yun Zhao, Joo Hye Song, Song Liu, Ninghai Wang, Cox Terhorst, Arlene H. Sharpe, Megha Basavappa, Kate L. Jeffrey, Hans Christian Reinecker

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalNature immunology
Volume15
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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