RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

Derek W. Trobaugh, Christina L. Gardner, Chengqun Sun, Andrew D. Haddow, Eryu Wang, Elik Chapnik, Alexander Mildner, Scott Weaver, Kate D. Ryman, William B. Klimstra

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3′ non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.

Original languageEnglish (US)
Pages (from-to)245-248
Number of pages4
JournalNature
Volume506
Issue number7487
DOIs
StatePublished - 2014

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RNA Viruses
MicroRNAs
Innate Immunity
Vertebrates
Eastern equine encephalitis virus
Virus Diseases
Myeloid Cells
Binding Sites
Tropism
Neurologic Manifestations
Nervous System Diseases
Culicidae
Antiviral Agents
Disease Progression
Genome
RNA
Viruses
Growth

ASJC Scopus subject areas

  • General

Cite this

Trobaugh, D. W., Gardner, C. L., Sun, C., Haddow, A. D., Wang, E., Chapnik, E., ... Klimstra, W. B. (2014). RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature, 506(7487), 245-248. https://doi.org/10.1038/nature12869

RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. / Trobaugh, Derek W.; Gardner, Christina L.; Sun, Chengqun; Haddow, Andrew D.; Wang, Eryu; Chapnik, Elik; Mildner, Alexander; Weaver, Scott; Ryman, Kate D.; Klimstra, William B.

In: Nature, Vol. 506, No. 7487, 2014, p. 245-248.

Research output: Contribution to journalArticle

Trobaugh, DW, Gardner, CL, Sun, C, Haddow, AD, Wang, E, Chapnik, E, Mildner, A, Weaver, S, Ryman, KD & Klimstra, WB 2014, 'RNA viruses can hijack vertebrate microRNAs to suppress innate immunity', Nature, vol. 506, no. 7487, pp. 245-248. https://doi.org/10.1038/nature12869
Trobaugh DW, Gardner CL, Sun C, Haddow AD, Wang E, Chapnik E et al. RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. Nature. 2014;506(7487):245-248. https://doi.org/10.1038/nature12869
Trobaugh, Derek W. ; Gardner, Christina L. ; Sun, Chengqun ; Haddow, Andrew D. ; Wang, Eryu ; Chapnik, Elik ; Mildner, Alexander ; Weaver, Scott ; Ryman, Kate D. ; Klimstra, William B. / RNA viruses can hijack vertebrate microRNAs to suppress innate immunity. In: Nature. 2014 ; Vol. 506, No. 7487. pp. 245-248.
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