title: Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA.
abstract: Mosquito-borne flaviviruses, including yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), profoundly affect human health. The successful transmission of these viruses to a human host depends on the pathogen's ability to overcome a potentially sterilizing immune response in the vector mosquito. Similar to other invertebrate animals and plants, the mosquito's RNA silencing pathway comprises its primary antiviral defense. Although a diverse range of plant and insect viruses has been found to encode suppressors of RNA silencing, the mechanisms by which flaviviruses antagonize antiviral small RNA pathways in disease vectors are unknown. Here we describe a viral suppressor of RNA silencing (VSR) encoded by the prototype flavivirus, YFV. We show that the YFV capsid (YFC) protein inhibits RNA silencing in the mosquito Aedes aegypti by interfering with Dicer. This VSR activity appears to be broadly conserved in the C proteins of other medically important flaviviruses, including that of ZIKV. These results suggest that a molecular "arms race" between vector and pathogen underlies the continued existence of flaviviruses in nature.
authors.affiliation: Department of Entomology, Texas A&M University, College Station, TX 77843.
authors.forename: Glady Hazitha
authors.initials: GH
authors.lastname: Samuel
authors.affiliation: Department of Entomology, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wiley
authors.affiliation: Department of Entomology, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
authors.forename: Atif
authors.initials: A
authors.lastname: Badawi
authors.affiliation: Department of Entomology, Texas A&M University, College Station, TX 77843.
authors.forename: Zach N
authors.initials: ZN
authors.lastname: Adelman
authors.affiliation: Department of Entomology, Texas A&M University, College Station, TX 77843; mylesk@tamu.edu.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Myles
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D009033:Culicidae / Q000235:genetics / Q000821:virology; D004199:Disease Vectors; D020868:Gene Silencing; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007303:Insect Vectors / Q000235:genetics / Q000821:virology; D012330:RNA, Double-Stranded / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D015004:Yellow Fever / Q000235:genetics* / Q000635:transmission / Q000821:virology; D015005:Yellow fever virus / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D036022:Capsid Proteins; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins
keywords: RNA interference; Zika virus; capsid; flavivirus; yellow fever virus