RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses1 . Thisis primarily attributed to the ease withwhich these virusesmutate to disrupt recognition and growth suppression by host miRNAs2,3. Here we report that the haematopoietic-cell-specific miRNA miR142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sitesin the 39 non-translated region ofits 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