ELF4 is critical for induction of type I interferon and the host antiviral response.

Authors:
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E.
In:
Source: Nat Immunol
Publication Date: (2013)
Issue: 14(12): 1237-46
Research Area:
Basic Research
Cells used in publication:
Embryonic fibroblast, mouse (MEF)primary
Species: mouse
Tissue Origin: embryo
Platform:
Nucleofector™ I/II/2b
Abstract
Induction of type I interferon is a central event of innate immunity, essential for host defense. Here we report that the transcription factor ELF4 is induced by type I interferon and upregulates interferon expression in a feed-forward loop. ELF4 deficiency leads to reduced interferon production, resulting in enhanced susceptibility to West Nile virus encephalitis in mice. After viral infection, ELF4 is recruited by STING, interacts with and is activated by the MAVS-TBK1 complex, and translocates into the nucleus to bind interferon promoters. Cooperative binding with ELF4 increases the binding affinity of interferon regulatory factors IRF3 and IRF7, which is mediated by EICE elements. Thus, in addition to identifying a regulator of innate immune signaling, we uncovered a role for EICE elements in interferon transactivation.