Journal article
RNA viruses can hijack vertebrate microRNAs to suppress innate immunity
Nature, Vol.506(7487), pp.245-+
Feb/2014
Abstract
Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses(1). This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs(2,3). 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.
Details
- Title
- RNA viruses can hijack vertebrate microRNAs to suppress innate immunity
- Creators
- Derek W. Trobaugh (null)Christina L. Gardner (null)Chengqun Sun (null)Andrew D. Haddow (null)Eryu Wang (null)Elik Chapnik (null) - 972WIS_INST___111Alexander Mildner (null) - The Weizmann Institute of ScienceScott C. Weaver (null)Kate D. Ryman (null)William B. Klimstra (null)
- Resource Type
- Journal article
- Publication Details
- Nature, Vol.506(7487), pp.245-+; Feb/2014
- Number of pages
- 15
- Language
- English
- DOI
- https://doi.org/10.1038/nature12869
- Grant note
- National Institutes of Health (NIH) [AI049820-10, AI060525-08, AI083383, AI095436]; National Institute of Allergy and Infectious Diseases through the Pacific Northwest Regional Centers for Excellence in Biodefense and Emerging Infectious Diseases Research [U54 AI081680]We thank M. Dunn for excellent technical support, and M. Diamond for reading of the manuscript. This work was supported by National Institutes of Health (NIH) training grants AI049820-10 and AI060525-08 (D. W. T.), research grants AI083383 and AI095436 (W. B. K.) and a Project Grant (K. D. R.) from National Institute of Allergy and Infectious Diseases through the Pacific Northwest Regional Centers for Excellence in Biodefense and Emerging Infectious Diseases Research (U54 AI081680). The views expressed are those of the authors and do not necessarily represent the views of the NIH._ALMAME_DELIMITER_
- Record Identifier
- 993266251903596
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