title: ELF4 is critical for induction of type I interferon and the host antiviral response.
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.
authors.affiliation: Section of Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Fuping
authors.initials: F
authors.lastname: You
authors.forename: Penghua
authors.initials: P
authors.lastname: Wang
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yang O
authors.initials: YO
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Wendy
authors.initials: W
authors.lastname: Walker
authors.forename: Richard
authors.initials: R
authors.lastname: Sutton
authors.forename: Ruth
authors.initials: R
authors.lastname: Montgomery
authors.forename: Rongtuan
authors.initials: R
authors.lastname: Lin
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000276:immunology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000276:immunology* / Q000502:physiology; D000099197:STING Protein
chemical_list: D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta; D008565:Membrane Proteins; D014157:Transcription Factors; C491779:Elf4 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein