title: Infectivity of West Nile/dengue chimeric viruses for West Nile and dengue mosquito vectors.
abstract: West Nile virus (WN), an agent of significant human and veterinary disease, is endemic in the Old World and rapidly spreading throughout the Americas. Vaccines are needed to halt the geographic expansion of this virus and prevent disease where it is established. However, to preclude introduction of a vaccine virus into the environment, a live attenuated WN vaccine should have low potential for transmission by mosquitoes. A chimeric WN vaccine candidate was previously generated by replacing the membrane and envelope structural protein genes of recombinant dengue type 4 virus (rDEN4) with those of WN; a derivative of this virus, WN/DEN4-3'delta30, contains a 30-nucleotide deletion in the 3' untranslated region. To assess the potential for transmission by mosquitoes of these vaccine candidates, the ability of each chimeric virus to infect the mosquito midgut, disseminate to the head, and pass into the saliva was compared to that of their wild-type parental WN and DEN4 viruses in three vector species. The WN/DEN4 chimeric viruses were significantly attenuated in both Culex tarsalis, a vector able to transmit WN but not dengue, and in Ae. aegypti, a vector able to transmit dengue but not WN. However, the chimeric viruses were as infectious as either wild-type virus for Ae. albopictus, a vector able to transmit both dengue and WN. These results indicate that chimerization caused a contraction in vector host range rather than universal attenuation for mosquitoes per se. This restriction in potential vectors renders it less likely that WN/DEN4 and WN/DEN4-3'delta30 would be transmitted from vaccinees to mosquitoes.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. khanley@nmsu.edu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Hanley
authors.forename: Laura B
authors.initials: LB
authors.lastname: Goddard
authors.forename: Lara E
authors.initials: LE
authors.lastname: Gilmore
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Scott
authors.forename: James
authors.initials: J
authors.lastname: Speicher
authors.forename: Brian R
authors.initials: BR
authors.lastname: Murphy
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Pletnev
mesh_terms: D000330:Aedes / Q000821:virology; D000818:Animals; D002522:Chlorocebus aethiops; D003465:Culex / Q000821:virology; D009033:Culicidae / Q000821:virology*; D003715:Dengue / Q000517:prevention & control / Q000635:transmission*; D003716:Dengue Virus / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007303:Insect Vectors / Q000821:virology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013045:Species Specificity; D014613:Vaccines, Attenuated / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology; D014901:West Nile Fever / Q000517:prevention & control / Q000635:transmission*; D014902:West Nile virus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines