title: A single positively selected West Nile viral mutation confers increased virogenesis in American crows.
abstract: West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species.
authors: Center for Vector-Borne Diseases and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA. acbrault@ucdavis.edu
authors: Aaron C
authors: AC
authors: Brault
authors: Claire Y-H
authors: CY
authors: Huang
authors: Stanley A
authors: SA
authors: Langevin
authors: Richard M
authors: RM
authors: Kinney
authors: Richard A
authors: RA
authors: Bowen
authors: Wanichaya N
authors: WN
authors: Ramey
authors: Nicholas A
authors: NA
authors: Panella
authors: Edward C
authors: EC
authors: Holmes
authors: Ann M
authors: AM
authors: Powers
authors: Barry R
authors: BR
authors: Miller
mesh_terms: D000569:Americas; D019943:Amino Acid Substitution; D000818:Animals; D001715:Bird Diseases / Q000821:virology*; D046368:Crows / Q000821:virology*; D019143:Evolution, Molecular; D016679:Genome, Viral; D005843:Geography; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D020365:RNA Helicases / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014902:West Nile virus / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
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