GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses.
- Resource Type
- Article
- Authors
- Chiang, Hao-Sen; Zhao, Yun; Song, Joo-Hye; Liu, Song; Wang, Ninghai; Terhorst, Cox; Sharpe, Arlene H; Basavappa, Megha; Jeffrey, Kate L; Reinecker, Hans-Christian
- Source
- Nature Immunology. Jan2014, Vol. 15 Issue 1, p63-71. 9p.
- Subject
- *MICROTUBULES
*NUCLEIC acids
*ANTIVIRAL agents
*INTESTINAL diseases
*INFLAMMATION
*BIOMOLECULES
*VIRUS diseases
- Language
- ISSN
- 1529-2908
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. [ABSTRACT FROM AUTHOR]