title: RNA viruses can hijack vertebrate microRNAs to suppress innate immunity.
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.
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Trobaugh
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Gardner
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Chengqun
authors.initials: C
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Haddow
authors.affiliation: 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.
authors.forename: Eryu
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Elik
authors.initials: E
authors.lastname: Chapnik
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.affiliation: 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.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Ryman
authors.affiliation: Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Klimstra
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D018354:Alphavirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D006224:Cricetinae; D009033:Culicidae / Q000821:virology; D004195:Disease Models, Animal; D004663:Encephalitis Virus, Eastern Equine / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology; D057131:Immune Evasion / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D007303:Insect Vectors / Q000821:virology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000821:virology; D009928:Organ Specificity; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse