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Nat Genet. 2007 Sep;39(9):1162-6. Epub 2007 Aug 12.

A single positively selected West Nile viral mutation confers increased virogenesis in American crows.

Author information

1
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

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.

PMID:
17694056
PMCID:
PMC2291521
DOI:
10.1038/ng2097
[Indexed for MEDLINE]
Free PMC Article

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