title: Evidence for ribosomal frameshifting and a novel overlapping gene in the genomes of insect-specific flaviviruses.
abstract: Flaviviruses have a positive-sense, single-stranded RNA genome of approximately 11 kb, encoding a large polyprotein that is cleaved to produce approximately 10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon overlapping gene (designated fifo) conserved throughout these insect-specific flaviviruses and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3'-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.
authors.affiliation: BioSciences Institute, University College Cork, Cork, Ireland. Electronic address: a.firth@ucc.ie.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Firth
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. Electronic address: blitvich@iastate.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Blitvich
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA. Electronic address: nwills@genetics.utah.edu.
authors.forename: Norma M
authors.initials: NM
authors.lastname: Wills
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA. Electronic address: clm@iastate.edu.
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Miller
authors.affiliation: BioSciences Institute, University College Cork, Cork, Ireland; Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA. Electronic address: j.atkins@ucc.ie.
authors.forename: John F
authors.initials: JF
authors.lastname: Atkins
mesh_terms: D000330:Aedes / Q000821:virology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003062:Codon / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D003465:Culex / Q000821:virology; D005416:Flavivirus / Q000235:genetics*; D018965:Frameshifting, Ribosomal / Q000235:genetics*; D005807:Genes, Overlapping / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics
chemical_list: D003062:Codon; D014764:Viral Proteins