Letter abstract


Nature Genetics 39, 1162 - 1166 (2007)
Published online: 12 August 2007 | doi:10.1038/ng2097

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

Aaron C Brault1,2, Claire Y-H Huang2, Stanley A Langevin1, Richard M Kinney2, Richard A Bowen3, Wanichaya N Ramey1, Nicholas A Panella2, Edward C Holmes4,5, Ann M Powers2 & Barry R Miller2

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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.

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  1. Center for Vector-Borne Diseases and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
  2. Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, US Department of Health and Human Services, Fort Collins, Colorado 80522, USA.
  3. Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
  4. Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  5. Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA.

Correspondence to: Aaron C Brault1,2 e-mail: acbrault@ucdavis.edu



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