title: NS1' of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness.
abstract: Flavivirus NS1 is a nonstructural protein involved in virus replication and regulation of the innate immune response. Interestingly, a larger NS1-related protein, NS1', is often detected during infection with the members of the Japanese encephalitis virus serogroup of flaviviruses. However, how NS1' is made and what role it performs in the viral life cycle have not been determined. Here we provide experimental evidence that NS1' is the product of a -1 ribosomal frameshift event that occurs at a conserved slippery heptanucleotide motif located near the beginning of the NS2A gene and is stimulated by a downstream RNA pseudoknot structure. Using site-directed mutagenesis of these sequence elements in an infectious clone of the Kunjin subtype of West Nile virus, we demonstrate that NS1' plays a role in viral neuroinvasiveness.
authors.affiliation: Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
authors.forename: Ezequiel Balmori
authors.initials: EB
authors.lastname: Melian
authors.forename: Edward
authors.initials: E
authors.lastname: Hinzman
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nagasaki
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Firth
authors.forename: Norma M
authors.initials: NM
authors.lastname: Wills
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Nouwens
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Blitvich
authors.forename: Jason
authors.initials: J
authors.lastname: Leung
authors.forename: Anneke
authors.initials: A
authors.lastname: Funk
authors.forename: John F
authors.initials: JF
authors.lastname: Atkins
authors.forename: Roy
authors.initials: R
authors.lastname: Hall
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D018965:Frameshifting, Ribosomal; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: C100315:NS1 protein, Flavivirus; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins