Biological properties of chimeric West Nile viruses.
Recently, we have described a lineage 2 attenuated WN virus suitable for the development of a live WN vaccine. To design vaccine candidates with an improved immunogenicity, we assembled an infectious clone of the NY99 strain and created several chimeric constructs with reciprocal exchanges of structural protein genes between attenuated W956 and virulent NY99 and investigated their biological properties. Our data indicated that, while the growth rates of NY99 and chimeric viruses in tissue culture are determined primarily by properties of the structural proteins, determinants responsible for a highly cytopathic phenotype of NY99 or lack thereof for W956 are located within the nonstructural protein region of the WN genome. The high virulence of NY99 and the attenuated phenotype of W956 were found to be associated with determinants in the nonstructural region. Chimeric viruses carrying the NY99 structural proteins were attenuated in neuroinvasiveness and demonstrated an immunogenicity superior to W956.
Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Ave., Lawrence, KS 66045, USA.
Victoria
V
Borisevich
Alexey
A
Seregin
Ryan
R
Nistler
David
D
Mutabazi
Vladimir
V
Yamshchikov
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000235:genetics; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005814:Genes, Viral; D007928:Lethal Dose 50; D051379:Mice; D009500:Neutralization Tests; D011995:Recombination, Genetic; D016019:Survival Analysis; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000032:analysis; D015678:Viral Structural Proteins / Q000235:genetics / Q000502:physiology; D014774:Virulence / Q000235:genetics; D014779:Virus Replication / Q000235:genetics; D014902:West Nile virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*
D000914:Antibodies, Viral; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D015678:Viral Structural Proteins