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.
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References
Hayes, E.B. Epidemiology and transmission dynamics of west nile virus disease. Emerg. Infect. Dis. 11, 1167–1173 (2005).
Sejvar, J.J. West Nile virus and “poliomyelitis”. Neurology 63, 206–207 (2004).
Solomon, T. & Ravi, V. Acute flaccid paralysis caused by West Nile virus. Lancet Infect. Dis. 3, 189–190 (2003).
Steele, K.E. et al. Pathology of fatal West Nile virus infections in native and exotic birds during the 1999 outbreak in New York City, New York. Vet. Pathol. 37, 208–224 (2000).
Weiss, D. et al. Clinical findings of West Nile virus infection in hospitalized patients, New York and New Jersey, 2000. Emerg. Infect. Dis. 7, 654–658 (2001).
Brault, A.C. et al. Differential virulence of West Nile strains for American crows. Emerg. Infect. Dis. 10, 2161–2168 (2004).
Reisen, W.K. et al. Role of corvids in epidemiology of west Nile virus in southern California. J. Med. Entomol. 43, 356–367 (2006).
Langevin, S.A., Arroyo, J., Monath, T.P. & Komar, N. Host-range restriction of chimeric yellow fever-West Nile vaccine in fish crows (Corvus ossifragus). Am. J. Trop. Med. Hyg. 69, 78–80 (2003).
Kinney, R.M. et al. Avian virulence and thermostable replication of the North American strain of West Nile virus. J. Gen. Virol. 87, 3611–3622 (2006).
Miller, B.R. et al. First field evidence for natural vertical transmission of West Nile virus in Culex univittatus complex mosquitoes from Rift Valley province, Kenya. Am. J. Trop. Med. Hyg. 62, 240–246 (2000).
Komar, N. et al. Experimental infection of North American birds with the New York 1999 strain of West Nile virus. Emerg. Infect. Dis. 9, 311–322 (2003).
Lanciotti, R.S. et al. Origin of the West Nile virus responsible for an outbreak of encephalitis in the northeastern United States. Science 286, 2333–2337 (1999).
Charrel, R.N. et al. Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe. Virology 315, 381–388 (2003).
Eidson, M. “Neon needles” in a haystack: the advantages of passive surveillance for West Nile virus. Ann. NY Acad. Sci. 951, 38–53 (2001).
Kramer, L.D. & Bernard, K.A. West Nile virus in the western hemisphere. Curr. Opin. Infect. Dis. 14, 519–525 (2001).
Langevin, S.A., Brault, A.C., Panella, N.A., Bowen, R.A. & Komar, N. Variation in virulence of West Nile virus strains for house sparrows (Passer domesticus). Am. J. Trop. Med. Hyg. 72, 99–102 (2005).
Reisen, W.K., Fang, Y. & Martinez, V.M. Avian host and mosquito (Diptera: Culicidae) vector competence determine the efficiency of West Nile and St. Louis encephalitis virus transmission. J. Med. Entomol. 42, 367–375 (2005).
Day, J.F. & Edman, J.D. Malaria renders mice susceptible to mosquito feeding when gametocytes are most infective. J. Parasitol. 69, 163–170 (1983).
Day, J.F. & Edman, J.D. The importance of disease induced changes in mammalian body temperature to mosquito blood feeding. Comp. Biochem. Physiol. A 77, 447–452 (1984).
Lipsitch, M. & Moxon, E.R. Virulence and transmissibility of pathogens: what is the relationship? Trends Microbiol. 5, 31–37 (1997).
Ewald, P.W. Host-parasite relations, vectors, and the evolution of disease severity. Annu. Rev. Ecol. Syst. 14, 465–485 (1983).
Work, T.H., Hurlbut, H.S. & Taylor, R.M. Indigenous wild birds of the Nile Delta as potential West Nile virus circulating reservoirs. Am. J. Trop. Med. Hyg. 4, 872–888 (1955).
Malkinson, M. & Banet, C. The role of birds in the ecology of West Nile virus in Europe and Africa. Curr. Top. Microbiol. Immunol. 267, 309–322 (2002).
Work, T.H., Hurlbut, H.S. & Taylor, R.M. Isolation of West Nile virus from hooded crow and rock pigeon in the Nile delta. Proc. Soc. Exp. Biol. Med. 84, 719–722 (1953).
Deardorff, E. et al. Introductions of West Nile virus strains to Mexico. Emerg. Infect. Dis. 12, 314–318 (2006).
Swofford, D. Phylogenetics Analysis Using Parsimony; Version 4 (Sinauer Associates, Sunderland, Massachusetts, 2003).
Pond, S.L. & Frost, S.D. Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21, 2531–2533 (2005).
Bakonyi, T., Hubalek, Z., Rudolf, I. & Nowotny, N. Novel flavivirus or new lineage of West Nile virus, central Europe. Emerg. Infect. Dis. 11, 225–231 (2005).
Acknowledgements
We thank C. Cope of the Kansas Department of Wildlife Resources (Wichita, Kansas) and T. Janousek for their assistance with crow trapping and K. Bird, R. McLean and L. Clark of the US Department of Agriculture Wildlife Health Center (Fort Collins, Colorado) for assistance with avian housing. We thank W. Reisen and C. Barker for their assistance with statistical analyses. Trapping of AMCRs was performed under US Fish and Wildlife Scientific Collecting Permit number MB-032526, and experimental inoculations were performed under Centers for Disease Control and Prevention IACUC protocol numbers 02-26-012-MSA and 03-13-013-MSA, CSU IACUC approval 02-058A and UC Davis IACUC protocol number 11279. Funding for these studies was provided by the US Centers for Disease Control and Prevention (CI000235), the US National Institutes of Health (AI061822) and the Pacific Southwest Regional Center for Excellence (U54 AI065359). The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.
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This study was designed by A.C.B., R.M.K., A.M.P. and B.R.M. Mutant constructions were produced by C.Y.-H.H., R.M.K., S.A.L. and W.N.R. Avian infections were performed by R.A.B. and N.A.P. Viral titrations were performed by S.A.L., N.A.P., W.N.R. with assistance from A.M.P. Positive selection analyses were performed by E.C.H.
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Brault, A., Huang, CH., Langevin, S. et al. A single positively selected West Nile viral mutation confers increased virogenesis in American crows. Nat Genet 39, 1162–1166 (2007). https://doi.org/10.1038/ng2097
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DOI: https://doi.org/10.1038/ng2097
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