title: Construction of yellow fever/St. Louis encephalitis chimeric virus and the use of chimeras as a diagnostic tool.
abstract: St. Louis encephalitis (SLE) and West Nile (WN) flaviviruses are genetically closely related and cocirculate in the United States. Virus neutralization tests provide the most specific means for serodiagnosis of infections with these viruses. However, use of wild-type SLE and WN viral strains for laboratory testing is constrained by the biocontainment requirements. We constructed two highly attenuated yellow fever (YF) virus chimeras that contain the premembrane-envelope (prM-E) protein genes from the virulent MSI-7 (isolated in the United States) or the naturally attenuated CorAn9124 (Argentina) SLE strains. The YF/SLE (CorAn version) virus and the previously constructed YF/WN chimera were shown to specifically distinguish between confirmed human SLE and WN cases in a virus neutralization test using patient sera. These chimeras have the potential for use as diagnostic reagents and vaccines against SLE and WN.
authors.affiliation: Acambis Inc., 38 Sidney Street, Cambridge, MA 02139, USA. konstantin.pugachev@acambis.com
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Pugachev
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
authors.forename: Fred
authors.initials: F
authors.lastname: Mitchell
authors.forename: Simeon W
authors.initials: SW
authors.lastname: Ocran
authors.forename: Megan
authors.initials: M
authors.lastname: Parsons
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Johnson
authors.forename: Olga L
authors.initials: OL
authors.lastname: Kosoy
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lanciotti
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Trent
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001118:Argentina / Q000453:epidemiology; D003465:Culex / Q000821:virology; D004665:Encephalitis Virus, St. Louis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D004674:Encephalitis, St. Louis / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D005814:Genes, Viral / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016415:Sequence Alignment; D014481:United States / Q000453:epidemiology; D014765:Viral Vaccines / Q000138:chemical synthesis* / Q000627:therapeutic use; D015004:Yellow Fever / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D015005:Yellow fever virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines