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Nat Immunol. 2011 Jun 5;12(7):624-30. doi: 10.1038/ni.2048.

IFIT1 is an antiviral protein that recognizes 5'-triphosphate RNA.

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  • 1Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.

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.

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PMID:
21642987
[PubMed - indexed for MEDLINE]
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