A viral RNA structural element alters host recognition of nonself RNA

Jennifer L. Hyde, Christina L. Gardner, Taishi Kimura, James P. White, Gai Liu, Derek W. Trobaugh, Cheng Huang, Marco Tonelli, Slobodan Paessler, Kiyoshi Takeda, William B. Klimstra, Gaya K. Amarasinghe, Michael S. Diamond

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)783-787
Number of pages5
JournalScience
Volume343
Issue number6172
DOIs
StatePublished - 2014

ASJC Scopus subject areas

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    Hyde, J. L., Gardner, C. L., Kimura, T., White, J. P., Liu, G., Trobaugh, D. W., Huang, C., Tonelli, M., Paessler, S., Takeda, K., Klimstra, W. B., Amarasinghe, G. K., & Diamond, M. S. (2014). A viral RNA structural element alters host recognition of nonself RNA. Science, 343(6172), 783-787. https://doi.org/10.1126/science.1248465