GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses
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CitationChiang, Hao-Sen, Yun Zhao, Joo-Hye Song, Song Liu, Ninghai Wang, Cox Terhorst, Arlene H. Sharpe, Megha Basavappa, Kate L. Jeffrey, and Hans-Christian Reinecker. 2014. “GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.” Nature immunology 15 (1): 63-71. doi:10.1038/ni.2766. http://dx.doi.org/10.1038/ni.2766.
AbstractDetailed 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 and Mda5-dependent phosphorylation of IRF3 and induction of interferon-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.
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