tetano
Editor, Senior Moderator
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
Nature Immunology
(2013)
doi:10.1038/ni.2766
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.
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2766.html
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
Nature Immunology
(2013)
doi:10.1038/ni.2766
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.
http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2766.html