Journal
SCIENCE
Volume 343, Issue 6172, Pages 783-787Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1248465
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Funding
- NIH [U19 AI083019, R01 AI104972, R01 AI083383, AI049820, P41RR02301, P41GM66326]
- Institute for Human Infections and Immunity, University of Texas Medical Branch [UL1TR000071]
- Grants-in-Aid for Scientific Research [24390120] Funding Source: KAKEN
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Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.
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