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Nature. 2014 Feb 13;506(7487):245-8. doi: 10.1038/nature12869. Epub 2013 Dec 18.

RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.

Author information

1
Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
2
Institute for Human Infections and Immunity, Center for Biodefense and Emerging Infectious Diseases, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
3
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
4
Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.

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.

PMID:
24352241
PMCID:
PMC4349380
DOI:
10.1038/nature12869
[Indexed for MEDLINE]
Free PMC Article

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