title: Virulence determinants between New York 99 and Kunjin strains of West Nile virus.
abstract: An attenuated Australian strain of West Nile virus (WNV), Kunjin (KUN), shares ~98% amino acid homology with the pathogenic New York 99 NY99 strain (NY99). To investigate the viral factors involved in NY99 virulence we generated an infectious cDNA clone of the WNV NY99 4132 isolate from which virus was recovered and was shown to be indistinguishable from the parental isolate. We then introduced the regions of the NY99 non-structural (NS) proteins and/or untranslated regions (UTRs) into the KUN backbone. Chimeric KUN viruses containing NY99 5'UTR and the parts of NS coding region were more virulent in mice than parental KUN virus. Chimeric NY99 viruses, containing KUN NS2A protein with alanine 30 to proline substitution were significantly less cytopathic in cells and less virulent in mice. Our results identify the 5'UTR and NS proteins as WNV virulence determinants and confirm a role for the NS2A in WNV cytopathicity and virulence.
authors.affiliation: Centre for Infectious Disease Research, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Audsley
authors.forename: Judith
authors.initials: J
authors.lastname: Edmonds
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.forename: Vlad
authors.initials: V
authors.lastname: Mokhonov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Mokhonova
authors.forename: Ezequeil Balmori
authors.initials: EB
authors.lastname: Melian
authors.forename: Natalie
authors.initials: N
authors.lastname: Prow
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Khromykh
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005818:Genetic Engineering; D007928:Lethal Dose 50; D051379:Mice; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D012376:Rodent Diseases / Q000473:pathology / Q000821:virology; D017422:Sequence Analysis, DNA; D016019:Survival Analysis; D010948:Viral Plaque Assay; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*; D014901:West Nile Fever / Q000473:pathology / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D012367:RNA, Viral; D037521:Virulence Factors