title: A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity.
abstract: Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.3-0.5 kb derived from the 3' untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3' untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.
authors.affiliation: School of Molecular and Microbial Sciences, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Gorben P
authors.initials: GP
authors.lastname: Pijlman
authors.forename: Anneke
authors.initials: A
authors.lastname: Funk
authors.forename: Natasha
authors.initials: N
authors.lastname: Kondratieva
authors.forename: Jason
authors.initials: J
authors.lastname: Leung
authors.forename: Shessy
authors.initials: S
authors.lastname: Torres
authors.forename: Lieke
authors.initials: L
authors.lastname: van der Aa
authors.forename: Wen Jun
authors.initials: WJ
authors.lastname: Liu
authors.forename: Ann C
authors.initials: AC
authors.lastname: Palmenberg
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D005416:Flavivirus / Q000472:pathogenicity*; D051379:Mice; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D022661:RNA, Untranslated / Q000096:biosynthesis*; D012367:RNA, Viral / Q000096:biosynthesis*; D012260:Ribonucleases / Q000378:metabolism*; D010948:Viral Plaque Assay
chemical_list: D020413:3' Untranslated Regions; D022661:RNA, Untranslated; D012367:RNA, Viral; D012260:Ribonucleases