title: IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA.
abstract: Antiviral innate immunity relies on the recognition of microbial structures. One such structure is viral RNA that carries a triphosphate group on its 5' terminus (PPP-RNA). By an affinity proteomics approach with PPP-RNA as the 'bait', we found that the antiviral protein IFIT1 (interferon-induced protein with tetratricopeptide repeats 1) mediated binding of a larger protein complex containing other IFIT family members. IFIT1 bound PPP-RNA with nanomolar affinity and required the arginine at position 187 in a highly charged carboxy-terminal groove of the protein. In the absence of IFIT1, the growth and pathogenicity of viruses containing PPP-RNA was much greater. In contrast, IFIT proteins were dispensable for the clearance of pathogens that did not generate PPP-RNA. On the basis of this specificity and the great abundance of IFIT proteins after infection, we propose that the IFIT complex antagonizes viruses by sequestering specific viral nucleic acids.
authors.affiliation: Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pichlmair
authors.forename: Caroline
authors.initials: C
authors.lastname: Lassnig
authors.forename: Carol-Ann
authors.initials: CA
authors.lastname: Eberle
authors.forename: Maria W
authors.initials: MW
authors.lastname: Górna
authors.forename: Christoph L
authors.initials: CL
authors.lastname: Baumann
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Burkard
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bürckstümmer
authors.forename: Adrijana
authors.initials: A
authors.lastname: Stefanovic
authors.forename: Sigurd
authors.initials: S
authors.lastname: Krieger
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.forename: Friedemann
authors.initials: F
authors.lastname: Weber
authors.forename: Jacques
authors.initials: J
authors.lastname: Colinge
authors.forename: Mathias
authors.initials: M
authors.lastname: Müller
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012367:RNA, Viral / Q000276:immunology*; D016601:RNA-Binding Proteins; D014780:Viruses / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C484290:IFIT1 protein, human; C092573:Ifit1 protein, mouse; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D001120:Arginine