title: The West Nile virus mutant spectrum is host-dependant and a determinant of mortality in mice.
abstract: To define the impact of mosquitoes and birds on intrahost WNV population dynamics, the mutant spectra that arose as a result of 20 serial in vivo passages in Culex pipiens and young chickens were examined. Genetically homogeneous WNV was serially passaged 20 times in each host. Genetic diversity was greater in mosquito-passaged WNV compared to chicken-passaged WNV. Changes in the viral consensus sequence occurred in WNV passaged in mosquitoes earlier and more frequently than in chicken-passaged WNV. Analysis of synonymous and nonsynonymous variation suggested that purifying selection was relaxed during passage in mosquitoes. Mortality in mice was significantly negatively correlated with the size of the WNV mutant spectrum. These studies suggest that mosquitoes serve as sources for WNV genetic diversity, that birds are selective sieves, and that both the consensus sequence and the mutant spectrum contribute to WNV phenotype.
authors.affiliation: The Arbovirus Laboratories, Wadsworth Center, New York State Department of Health, 5668 State Farm Rd., Slingerlands, NY 12159, USA.
authors.forename: Greta V S
authors.initials: GV
authors.lastname: Jerzak
authors.forename: Kristen
authors.initials: K
authors.lastname: Bernard
authors.forename: Laura D
authors.initials: LD
authors.lastname: Kramer
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ebel
mesh_terms: D000818:Animals; D002645:Chickens / Q000821:virology; D003465:Culex / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D014644:Genetic Variation; D016679:Genome, Viral; D051379:Mice; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014901:West Nile Fever / Q000401:mortality* / Q000473:pathology / Q000821:virology*; D014902:West Nile virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*
chemical_list: D012367:RNA, Viral