IFIT1 is an antiviral protein that recognizes 5′-triphosphate RNA

Andreas Pichlmair, Caroline Lassnig, Carol Ann Eberle, Maria W. Górna, Christoph L. Baumann, Thomas R. Burkard, Tilmann Búrckstúmmer, Adrijana Stefanovic, Sigurd Krieger, Keiryn L. Bennett, Thomas Rúlicke, Friedemann Weber, Jacques Colinge, Mathias Múller, Giulio Superti-Furga

Research output: Contribution to journalArticlepeer-review

391 Scopus citations

Abstract

Antiviral innate immunity relies on the recognition of microbial structures. One such structure is viral RNA that carries a triphosphate group on its 5ĝ€2 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.

Original languageEnglish
Pages (from-to)624-630
Number of pages7
JournalNature Immunology
Volume12
Issue number7
DOIs
StatePublished - May 2011
Externally publishedYes

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